Survey
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FORM-I For PROPOSED EXPANSION OF EXISTING BULK DRUGS AND BULK DRUG INTERMEDIATES MANUFACTURING UNIT of M/s. HEM-DEEP ORGANICS PVT. LTD. Plot No. 3801/2, GIDC Estate, Ankleshwar – 393 002, Dist. Bharuch, Gujarat, INDIA. APPENDIX I FORM 1 (I) Sr. No. 1. 2. 3. Basic Information Item Details M/s. Hem-Deep Organics Pvt. Ltd. 5(f) Capacity of Proposed Expansion of bulk Drugs and its intermediates: 737.5 MT/Month, Repacking: 100 MT/Month & Distillation: 200 MT/Month 4. Name of the Project/s S.No. in the Schedule Proposed capacity / area / length / tonnage to be handled/command area/lease area/number of wells to be drilled New/Expansion/Modernization Expansion 5. Existing capacity/area etc. Existing Capacity: 6 MT/Month 6. 7. Category of project i.e. ‘A’ or ‘B’ Does it attract the general condition? If yes, please specify. Does it attract the specific condition? If yes, please specify. Location Plot/Survey/Khasra No. Village Tehsil District State Nearest railway station/airport along with distance in kms. Nearest Town, city, District Headquarters along with distance in kms. Village Panchayats, Zilla Parishad, Municipal corporation, Local body (Complete postal addresses with telephone nos. to be given) Name of the applicant Registered address ‘A’ Yes. Located (Ankleshwar). N.A. 8. 9. 10. 11. 12. 13. 14. 15. Address for correspondence: Name Designation (Owner/Partner/CEO) Address Pin Code E-Mail Telephone No. in Critically Polluted Area Plot. No. 3801/2 GIDC Estate Ankleshwar - 393 002 Bharuch Gujarat Nearest Railway Station: Ankleshwar = 4 km Nearest Airport : Surat = 70 km Nearest Town: Ankleshwar = 4 km Nearest District Head Quarter: Bharuch = 15 km Notified Area Authority, Ankleshwar M/s. Hem-Deep Organics Pvt. Ltd. Plot. No. 3801/2, GIDC, Ankleshwar - 393 002, Dist: Bharuch, Gujarat, INDIA. Mr. Kamlesh Gami Partner M/s. Hem-Deep Organics Pvt. Ltd. Plot. No. 6012/1, GIDC, Ankleshwar - 393 002, Dist: Bharuch, Gujarat, INDIA. 393 002 [email protected] Tel. : +91-2646-226676 Mob.: +91 9824014578 16. 17. 18. 19. 20. 21. 22. 23. 24. Fax No. Details of Alternative Sites examined, if any location of these sites should be shown on a topo sheet. Interlinked Projects Whether separate application of interlinked project has been submitted? If Yes, date of submission If no., reason Whether the proposal involves approval/clearance under: If yes, details of the same and their status to be given. (a) The Forest (Conservation) Act, 1980? (b) The Wildlife (Protection) Act, 1972? (c) The C.R.Z Notification, 1991? Whether there is any Government order/policy relevant/relating to the site? Forest land involved (hectares) Whether there is any litigation pending against the project and/or land in which the project is propose to be set up? (a) Name of the Court (b) Case No. (c) Orders/directions of the Court, if any and its relevance with the proposed project. -No No Not applicable Not applicable Not applicable Not applicable as proposed expansion activity is going to occur within GIDC, Ankleshwar. No No No (II) Activity 1. Construction, operation or decommissioning of the Project involving actions, which will cause physical changes in the locality (topography, land use, changes in water bodies, etc.) Sr. No. Information/Checklist confirmation 1.1 Permanent or temporary change in land No use, land cover or topography including increase in intensity of land use (with respect to local land use plan) 1.2 Clearance of existing land, vegetation and buildings? Yes Minor site clearance activities shall be carried out to clear shrubs and weed. 1.3 1.4 Creation of new land uses? Pre-construction investigations e.g. bore houses, soil testing? No No --- 1.5 Construction works? Yes is 1.6 1.7 No No Yes Approved plan for construction attached as Annexure: 1. is No -- 1.10 1.11 1.12 1.13 Demolition works? Temporary sites used for construction workers or housing of construction workers? Above ground buildings, structures or Earthworks including linear structures, cut and fill or excavations Underground works including mining or tunneling? Reclamation works? Dredging? Offshore structures? Production and manufacturing Approved plan for construction attached as Annexure: 1. --- No No No Yes 1.14 Facilities for storage of goods or materials? Yes 1.15 Facilities for treatment or disposal of solid waste or liquid effluents? Yes ---List of Products is attached as Annexure: 2 and manufacturing process is attached as Annexure: 3. Dedicated storage area for storage of Raw Materials and finished products, solvents, etc. shall be provided. Effluent Treatment Plant will be installed to treat effluent so as to achieve the GPCB norms. Details of water consumption & effluent generation with segregation of effluent streams are attached as Annexure: 4. Details of proposed Effluent Treatment Plant are attached as Annexure: 5. Details of Hazardous waste generation and disposal is attached as Annexure: 6. 1.16 Facilities for long term housing of operational workers? New road, rail or sea traffic during construction or operation? New road, rail, air waterborne or other airports etc? No 1.8 1.9 1.17 1.18 Yes /No? Details thereof (with approximate quantities / rates, wherever possible) with source of information data Proposed expansion activity is going to occur within existing sit in GIDC estate, Ankleshwar. No -- No -- 1.19 1.20 1.21 1.22 1.23 Closure or diversion of existing transport routes or infrastructure leading to changes in traffic movements? New or diverted transmission lines or pipelines? Impoundment, damming, converting, realignment or other changes to the hydrology of watercourses or aquifers? Stream crossings? Abstraction or transfers or the water form ground or surface waters? No -- No No --- No Yes 1.24 Changes in water bodies or the land surface affecting drainage or run-off? No -No ground water shall be used. The requirement of raw water shall be met through GIDC Water Supply. -- 1.25 Transport of personnel or materials for construction, operation or decommissioning? No -- 1.26 Long-term dismantling or decommissioning or restoration works? Ongoing activity during decommissioning which could have an impact on the environment? Influx of people to an area in either temporarily or permanently? Introduction of alien species? Loss of native species of genetic diversity? Any other actions? No No There is no dismantling of any sort. Not applicable. No Impact on the Environment No -- No No No ---- 1.27 1.28 1.29 1.30 1.31 2. Use of Natural resources for construction or operation of the Project (such as land, water, materials or energy, especially any resources which are non-renewable or in short supply): Sr. No 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Information/checklist confirmation Yes/ No? Land especially undeveloped or agriculture land (ha) Water (expected source & competing users) unit: KLD No Yes Minerals (MT) Construction material -stone, aggregates, sand / soil (expected source MT) Forests and timber (source - MT) No Yes Energy including electricity and fuels source, competing users Unit: fuel (MT), energy (MW) Yes Any other natural resources appropriates standard units) No (use No Details there of (with approximate quantities/rates, wherever possible) with source of information data -Water requirement will be met through the GIDC Water Supply. Detailed water balance is given as Annexure – 4. Not applicable Company shall use Sand, stone, Cement and Structural Steel for Construction as required. No wood shall be used as construction material or as a fuel. Power required from GEB is 100 KVA (Existing) Power required from GEB will 500 KVA (Proposed) 1 D.G. Set = 250 KVA (Proposed) (For Emergency Only) Fuel: Natural Gas = 10 m3/Day(Existing) LDO = 500 Liter/Day (Existing) Agro Waste/Briquettes = 10 MT/Day (Proposed) HSD = 20 Liter/Hr (Proposed) (For Emergency Only) -- 3. Use, storage, transport, handling or production of substances or materials, which could be harmful to human health or the environment or raise concerns about actual or perceived risks to human health. Sr. No. Information / Checklist confirmation Yes/ No? 3.1 Use of substances or materials, which are hazardous (as per MSIHC rules) to human health or the environment (flora, fauna, and water supplies) Yes 3.2 Changes in occurrence of disease or affect disease vectors (e.g. insect or water borne diseases) Affect the welfare of people e.g. by changing living conditions? No 3.4 Vulnerable groups of people who could be affected by the project e.g. hospital patients, children, the elderly etc., No 3.5 Any other causes No 3.3 Details thereof (with approximate quantities / rates wherever possible) with source of information data Please refer Annexure : 8. Not applicable as site is located in GIDC, Ankleshwar. Not applicable as site is located in GIDC, Ankleshwar. No Not applicable as site is located in GIDC, Ankleshwar. -- 4. Production of solid wastes during construction or operation or decommissioning MT/month) Sr. No. Information/Checklist confirmation Yes/ No? 4.1 4.2 No No -- 4.7 Spoil, overburden or mine wastes Municipal waste (domestic and or commercial wastes) Hazardous wastes (as per Hazardous Waste Management Rules) Other industrial process wastes Surplus product Sewage sludge or other sludge from effluent treatment Construction or demolition wastes Details thereof (with approximate quantities / rates, wherever possible) with source of information data -- 4.8 4.9 4.10 4.11 Redundant machinery or equipment Contaminated soils or other materials Agricultural wastes Other solid wastes 4.3 4.4 4.5 4.6 Yes Please refer Annexure: 6 Yes No Yes Please refer Annexure: 6 -Please refer Annexure: 6 No Construction waste shall be utilized for leveling & land filling in the premises. ---Please refer Annexure: 6 No No No No 5. Release of pollutants or any hazardous, toxic or noxious substances to air (Kg/hr) Sr. No. Information/Checklist confirmation Yes/ No? 5.1 Emissions from combustion of fossil fuels From stationary or mobile sources Emissions from production processes Yes 5.2 Yes Details thereof (with approximate quantities/rates, wherever possible) with source of information data Details of flue & process gas emission are attached as Annexure: 7 Reactors shall be connected to common scrubber system. Details of emission levels from process are attached as Annexure: 7. 5.3 Emissions from materials handling including storage or transport Yes 5.4 Emissions from construction including plant and equipment activities No 5.5 Dust or odours from handling of materials including construction materials, sewage and waste No 5.6 5.7 Emissions from incineration of waste Emissions from burning of waste in open air (e.g. slash materials, construction debris) No No 5.8 Emissions from any other sources No Details of Air Pollution Control measures are attached as Annexure: 7 All liquid raw materials shall be procured in bulk tankers and shall be transferred through a closed circuit pipe lines by pumps. Solid raw material shall be handled in closed charging rooms with proper ventilation and charged through close pipeline into reactors. Utmost care will be taken during construction activity and water sprinklers shall be utilized whenever necessary. All the waste shall be stored in designated places and shall be transported to TSDF or Incineration Site in their own approved closed vehicles. 6. Generation of Noise and Vibration, and Emissions of Light and Heat: Sr. No. Information/Checklist confirmation Yes/ No? 6.1 From operation of equipment e.g. engines, ventilation plant, crushers Yes 6.2 From industrial or similar processes Yes 6.3 6.4 From construction or demolition From blasting or piling No No Details there of (with approximate Quantities /rates, wherever possible) With source of source of information data There are few activities due to which noise would be generated. The equipments resulting in noise generation are machinery of plant and Diesel generator. Adequate noise control measures will be provided whenever required. Proper and timely oiling, lubrication and preventive maintenance will be carried out for the machineries & equipments to reduce noise generation. Use of PPEs like ear plugs and ear muffs will be made compulsory near the high noise generating machines. Noise monitoring shall be done regularly in plant area. The D.G. Set will be installed in a closed room and provided with acoustic enclosure. The unit will carry out plantation in the proposed greenbelt within the premises which will prevent the noise pollution in surrounding area. All machinery / equipment shall be well maintained, shall have proper foundation with anti vibrating pads wherever applicable and noise levels will be within permissible limits. Acoustic enclosures shall be provided for DG set. 6.5 6.6 6.7 From construction or operational traffic From lighting or cooling systems From any other sources No No Yes Acoustic enclosures shall be provided for DG set. 7. Risks of contamination of land or water from releases of pollutants into the ground or into sewers, surface waters, groundwater, coastal waters or the sea: Sr. No Information/Checklist confirmation Yes/ No? 7.1 From handling, storage, use or spillage of hazardous materials Yes 7.2 From discharge of sewage or other effluents to water or the land (expected mode and place of discharge) By deposition of pollutants emitted to air into the land or into water From any other sources Is there a risk of long term build up of pollution in the environment from these sources? No 7.3 7.4 7.5 Details thereof (with approximate quantities / rates, wherever possible) with source of information data All the raw material shall be stored separately in designated storage area and safely. Bund walls shall be provided around raw materials storage tanks for containing any liquid spillage. Other materials shall be stored in bags / drums on pallets with concrete flooring and no spillage is likely to occur. Please refer Annexure : 8. No -- No No Not applicable Full- fledged Environmental Management System (EMS) will be installed. i.e. ETP, Air Pollution Control systems, Hazardous Waste Handling and Management as per norms, etc. which will eliminates the possibility of building up of pollution. 8. Risks of accident during construction or operation of the Project, which could affect human health or the environment: Sr. No 8.1 8.2 8.3 Information/Checklist confirmation From explosions, spillages, fires etc from storage, handling, use or production of hazardous substances From any other causes Could the project be affected by natural disasters causing environmental damage (e.g. floods, earthquakes, landslides, cloudburst etc)? Yes/ No? Yes No No Details thereof (with approximate quantities / rates, wherever possible) with source of information data The risk assessment will be carried out and all mitigative measures shall be taken to avoid accidents. Not applicable -- 9. Factors which should be considered (such as consequential development) which could lead to environmental effects or the potential for cumulative impacts with other existing or planned activities in the locality Sr. No. 9.1 9.2 9.3 9.4 Information/Checklist confirmation Lead to development of supporting. laities, ancillary development or development stimulated by the project which could have impact on the environment e.g.: * Supporting infrastructure (roads, power supply, waste or waste water treatment, etc.) • housing development • extractive industries • supply industries • other Lead to after-use of the site, which could have an impact on the environment Set a precedent for later developments Have cumulative effects due to proximity to Other existing or planned projects with similar effects Yes/ No? Yes No No No Details thereof (with approximate quantities / rates, wherever possible) with source of information data Site is located in Ankleshwar Industrial Area, having the entire required infrastructure. This industrial zone is having existing road infrastructure, power supply are to be utilized. Local people will be employed and no housing is required. Please refer Annexure – 9. -Not applicable The ETP of the company shall be designed such that the treated effluent conforms to the statutory requirement. (III) Environmental Sensitivity Sr. No 1 2 3 4 5 6 7 8 9 10 11 12 Information/Checklist confirmation Name / Aerial distance (within 25 km). Proposed Identity Project Location Boundary. Areas protected under international conventions No Site is located in Ankleshwar Industrial national or local legislation for their ecological, Area, Tal. Ankleshwar, Dist. Bharuch, landscape, cultural or other related value Gujarat. Areas which are important or sensitive for No Site is located in Ankleshwar Industrial Ecological reasons - Wetlands, watercourses or Area, Tal. Ankleshwar, Dist. Bharuch, other water bodies, coastal zone, biospheres, Gujarat. mountains, forests Areas used by protected, important or sensitive No Site is located in Ankleshwar Industrial species of flora or fauna for breeding, nesting, Area, Tal. Ankleshwar, Dist. Bharuch, foraging, resting, over wintering, migration Gujarat. Inland, coastal, marine or underground waters Yes River Narmada: 9 Km Amla Khadi: 5 Km State, National boundaries No -Routes or facilities used by the public for to No Not applicable recreation or other tourist, pilgrim areas. Defense installations Densely populated or built-up area Areas occupied by sensitive man-made land community facilities) Areas containing important, high quality or scarce resources (ground water resources, surface resources, forestry, agriculture, fisheries, tourism, tourism, minerals) Areas already subjected to pollution or environmental damage. (those where existing legal environmental standards are exceeded) Are as susceptible to natural hazard which could cause the project to present environmental problems (earthquakes, subsidence ,landslides, flooding erosion, or extreme or adverse climatic conditions) No NIL Yes No Bharuch city: 4 Lakh population No The project being in industrial area does not affect agricultural land. No Site is located in Ankleshwar Industrial Area, Tal. Ankleshwar, Dist. Bharuch, Gujarat. N.A. No I hereby given undertaking that the data and information given in the application and enclosures are true to the best of my knowledge and belief and I am aware that if any part of the data and information submitted is found to be false or misleading at any stage, the project will be rejected and clearance given, if any to the project will be revoked at our risk and cost. Date: July 10, 2017 Place: Ankleshwar NOTE: 1. The projects involving clearance under Coastal Regulation Zone Notification, 1991 shall submit with the application a C.R.Z. map duly demarcated by one of the authorized agencies, showing the project activities, w.r.t. C.R.Z. (at the stage of TOR) and the recommendations of the State Coastal Zone Management Authority (at the stage of EC). Simultaneous action shall also be taken to obtain the requisite clearance under the provisions of the C.R.Z. Notification, 1991 for the activities to be located in the CRZ. 2. The projects to be located within 10 km of the National Parks, Sanctuaries, Biosphere Reserves, Migratory Corridors of Wild Animals, the project proponent shall submit the map duly authenticated by Chief Wildlife Warden showing these features vis-à-vis the project location and the recommendations or comments of the Chief Wildlife Warden thereon (at the stage of EC). 3. All correspondence with the Ministry of Environment & Forests including submission of application for TOR/Environmental Clearance, subsequent clarifications, as may be required from time to time, participation in the EAC Meeting on behalf of the project proponent shall be made by the authorized signatory only. The authorized signatory should also submit a document in support of his claim of being an authorized signatory for the specific project. ANNEXURES LIST: 1 Plot layout 2 List of products with production capacity and raw materials 3 Brief manufacturing process, chemical reaction and mass balance 4 Details of water consumption and waste water generation 5 Details of effluent treatment plant 6 7 Details of hazardous/solid waste generation, management and disposal mode Details hazardous chemical storage facility 8 Details of air pollution sources and control measures 9 Socio - Economic impacts 10 Proposed Terms Of References 11 GIDC Plot Allotment Letter & GIDC Water Supply Letter 12 Membership Certificate of CETP, ETL-Ankleshwar for disposal of treated effluent 13 Membership Certificate of TSDF & Common Incinerator, BEILAnkleshwar ANNEXURE-1 PLOT LAYOUT ANNEXURE-2 LIST OF PRODUCTS WITH PRODUCTION CAPACITY (Existing and Proposed scenario) Sr. No. Products Existing Capacity (MT/Month) Additional CAS No. Total 1 Oxyclozanide 3.5 0 3.5 2277-92-1 2 Furosemide 2.5 0 2.5 5.0 54-31-9 100 100 123-92-2 0 100 100 105-68-0 0 -------------------------------------- 10 10 25 25 76824-35-6 14205-39-1 88150-62-3 93479-97-1 106649-95-0 76824-35-6 152751-57-0 845273-93-0 71550-12-4 7554-65-6 182815-44-7 93479-97-1 5579-84-0 106685-40-9 144701-48-4 175591-09-0 8068-28-8 147098-20-2 534-07-6 2114-02-5 117976-90-6 72956-09-3 169590-42-5 120202-66-6 134523-03-8 202409-33-4 137862-53-4 1197-18-8 59-30-3 189005-44-5 148553-50-8 79794-75-5 60142-96-3 54965-21-8 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 Diaminomethyleneamino (1-amino-1iminomethylene) thiomethyl thiozole dihydrochloride [ITU] N-Sulfomyl-3-chloropropionamide hydrochloride[IF] Famotidine Fomepizole Colsevelam hydrochloride Glimepiride Betahistine Dihydrochloride Adapalene Telmisartan Tapentadol Hydrochloride Colistimethate Sodium Rusvastatin Calcium 1-3 dichloro Acetone Gunylthiourea Rabeprazole Sodium Carvediol Celecoxib Clopidogrel Bisulfate Atoravastatin Calcium Etoricoxib Valsartan Tranexamic Acid Folic Acid Zolpidic Acid Pregabaline Chlorohexidine Base Benzarone Benzbromarone Zaltoprofen Ondansetron Hydrochloride Miconazole Nitrate Ecanazole Nitrate Desloratadine Loratidine Gabapentine Albendazole 39 40 41 42 43 44 45 46 47 48 49 50 51 52 (B) 60 61 62 63 64 64 Citrezine Hydrochloride Lasamide Pioglitazone Hydrochloride Mesalamine Febuxostat Itopride Hydrochloride Amodafinil Quetipine Fumrate Aripiprazole Amlodipine Besylate Nebivilol Hydrochloride Sevelamer Hydrochloride Sevelamer Carbonate Poly Allaylamine Hydrochloride Total (A) Distillation of Solvent (B) REPACKING Benzophenone (Repacking) Para Cresyl Phenyl Acetate (Repacking) Poly Allaylamine Hydrochloride (Repacking) Allaylamine (Repacking) Allaylamine Hydrochloride (Repacking) Micronization of Bulk Drugs/APIs (Famotidine, Amlodipine, Glibenclamide, Sevelamer HCl, Glimepride, Adapalene, ITU, IF, Colsevelam HCl, Furosemide, Telmisartan, Betahistine Dihydrochloride, Tapentadol HCl, etc.) Total (C) Total (A+B+C) --------------6.0 -- 500 737.5 200.0 500 743.5 200.0 100.0 100.0 100.0 1037.5 100.0 1043.5 ------ -- -6.0 83881-52-1 2736-23-4 112529-15-4 89-57-6 144060-53-7 122892-31-3 68693-11-8 111974-72-2 129722-12-9 111470-99-6 152520-56-4 106-27-4 103-45-7 122-70-3 LIST OF RAW MATERIALS AND CONSUMPTION: Sr. No. Raw Material 1. 2. 3. 4. 5. 6. Oxyclozanide 3,5,6 TCSA MCB Thionyl Chloride 2,4 DCAP Sodium Bicarbonate Acetone Furosemide Furfuryl Amine Lasamide Caustic Flake IPA Carbon Acetic Acid Diaminomethyleneamino (1-amino-1iminomethylene) thiomethyl thiozole dihydrochloride [ITU] 1,3 DCA Guanyl Thiourea Acetone Catalyst Thiourea Acetic Acid N-Sulfomyl-3-chloropropionamide hydrochloride [IF] Acrylonitrile Hydrogen Peroxide HCl (Gas) Sulfamide Acetone Famotidine ITU IF Methanol NaOH Water Acetic Acid Colsevelam hydrochloride Monoallylamine 2,2-dimethyl-2,2-azopropane dihydrochloride Concentrated Hydrochloric acid Methanol Polyallylamine Epichlorohydrin n-Decylchloride Quantity (MT/MT) 1.50 1.50 0.75 1.00 0.05 3.25 0.450 0.850 0.234 0.240 0.080 0.220 0.435 0.413 3.100 0.004 0.261 0.261 1.303 0.008 1.495 0.500 0.400 1.150 0.965 5.710 0.690 20.50 0.200 0.60 0.01 1.15 0.31 0.90 0.01 0.02 7. 8. 9. 10. 11. 12. Trimethylammoniumhexylchloride Sodium hydroxide Glimepiride 3 Ethyl methyl Pyrroline 2 Phenyl ethyl isocyanate Toluene Chloro Sulfonic Acid Ammonia Solution EDC Fomepizole Propanaldehyde Ethanol Hexane Phosphorus oxychloride Hydrazine Hydrate Potassium Carbonate Carbon Di isopropyl Ether N,N-Dimethyl Formamide Dichloro Methane Betahistine Dihydrochloride 2- vinyl pyridine Methylamine hydrochloride Chloroform Sodium hydroxide Acetic Acid IPA IPA HCl(20%) Adapalene Adamentanol Para Bromo Phenol THF Mg Turning MDC 6-Bromo-2-methyl naphthoate HCl Telmisartan 4-Amino 3- Methylbenzoic acid Conc. Sulphuric Acid Liq. Ammonia Methanol MDC TEA Butryl Chloride Sodium Bicarbonate Sodium Sulphate Hexane Fuming Nitric Acid Tapentadol Hydrochloride 0.02 0.45 0.40 0.40 0.15 1.00 3.10 0.30 1.31 0.015 0.015 3.45 1.10 0.75 0.15 0.02 0.01 0.03 0.63 0.80 0.23 0.45 0.06 0.01 1.38 0.48 0.30 0.025 0.06 0.04 0.72 1.32 1.484 1.423 2.968 0.06 0.03 0.01 1.287 0.153 0.387 0.02 4.050 13. 14. 3-methoxy propiophenone IPA Dimethyl Amine HCL Paraformadehyde Sodium Hydroxide MDC L (-) Dibenzoyl tartaric acid THF Mg Turning Ethyl Bromide Acetic Acid Ammonium Solution Ethyl Acetate Trifluroacetic anhydride Palladium Acetone HBr IPA HCl Colistimethate Sodium Colistin Sulphate Sodium Bicarbonate Sodium Carbonate Formaldehyde Sodium Bisulfite Acetic Acid Solvent Acetone Methanol Rusvastatin Calcium 4-Fluoro Benzaldehyde 4-Methyl-3-oxo-Pentatonic Acid Ethyl Ester Potassium Hydroxide Methyl Iodide Methanol 5-Methyl Iso Thio Urea 2,3-Dichloro-5,6-Dicyano Benzoquinone HMPA MDC Meta Chloro Peroxy Benzoic Acid Methyl Amine Ethanol Methane Sulfonyl Chloride Sodium Hydride (60%) Di Methoxy Ethane Hydrogen DIBAL-H Toluene 1.412 0.350 1.059 0.588 0.376 0.350 1.412 0.080 0.171 0.588 0.118 0.506 0.230 0.882 0.070 0.260 1.765 0.882 1.33 0.67 0.33 1.33 3.06 0.16 0.80 2.00 3.00 0.52 0.66 0.24 0.60 5.50 0.35 0.85 1.00 8.00 0.11 0.10 2.50 0.35 0.01 3.00 0.01 0.01 8.00 15. 16. 17. 18. Methyl(3R)-3-(tert butyl dimethyl silyloxy)-5oxo-6-triphenyl phosphoranylidene hexanoate Triethyl Amine N,N-Dimethyl Formamide Hydrogen Fluoride THF Ethyl Acetate Diethyl Methoxy Borane Sodium Borohydride Calcium Chloride 1-3 dichloro Acetone Epichlorohydrin HCl (30%) Sulfuric Acid (98%) Sodium Dichromate Gunylthiourea Phosphorus Penta Sulphide KOH Dicyanadiamide Sodium Hydro Sulphite Rabeprazole Sodium 2,3-Lutidine H2O2 (50%) Nitric Acid Acetic Acid 3-Methoxy 1-Propanol NaOH Toluene DMSO Acetic Anhydride HCl Thionyl Chloride MDC Sodium Sulphate 2-Mercaptobenzimidazole Ammonium Hydroxide Sodium Hypochlorite (8%) Acetone Sodium Hydro Sulphate MMA IPA Activated Carbon Carvediol 4-Hydroxy Carbazole Epichlorohydrin Hydrose Methanol 1.45 0.15 3.00 0.05 7.50 10.50 0.20 0.01 0.13 1.302 3.125 1.862 1.562 0.827 1.000 0.909 0.181 0.460 0.330 0.380 0.060 0.430 0.155 0.012 0.010 0.390 0.200 0.530 0.370 0.100 0.530 0.125 3.270 0.100 0.120 0.100 0.150 0.100 0.447 0.790 0.116 0.067 19. 20. 21. Ethyl Acetate Carbon Hyflo Monoethylene Glycol Dimethyl Ether 2-(2-Methoxy Phenoxy) Ethyl Amine Acetone Potassium Carbonate Oxalic Acid IPA Sodium Sulphate Ortho Phosphoric Acid Celecoxib 4 SPH Dione Deri Toluene Carbon Clopidogrel Bisulfate amino(2-chlorophenyl)acetic acid methanol Potassium salt MDC Liq. ammonia Thiophene-2-Ethanol p-toluene sulphonyl chloride Toluene Sodium hydroxide Acetonitrile Dipotassium phosphate Ethyl acetate HCL P-Formaldehyde MDC Liq. Ammonia Acetone Tartaric acid MDC Sodium carbonate Acetone Activated carbon Sulfuric acid Atoravastatin Calcium Ethyl-4-Cyano-3-hydroxy butanaote THF Diisopropyl amine N-Butyl Lithium 0.029 0.022 0.005 2.330 0.956 0.101 0.372 0.532 0.052 0.207 0.442 0.70 0.65 2.80 0.01 1.25 0.20 0.7 0.50 0.62 0.5 1.05 0.16 1.25 0.32 0.87 0.28 0.85 0.53 1.02 0.60 1.10 0.82 0.67 0.70 0.24 0.15 0.31 1.00 0.85 1.22 0.6 22. 23. Tert-Butyl acetate HCl Ethyl Acetate NaCl Methanol DEMB (50 % Soln) Sodium Borohydride Acetic Acid Dimethoxy Propane Methane Sulphonic Acid Sodium Bicarbonate n-Hexane Raney Nickel Pivalic Acid Toluene Activated Carbon Methyl Tert Butyl Etoricoxib Acetic Acid Acetone Ammonia Solution CPT-Phosphate D M Water Hydroxylamine Hydrochloride Hyflow Isopropyl Alcohol Ketosulfone Methanol Potassium Tertrabutoxide (KTB) Sodium Acetate Sodium Hydroxide Toluene THF Trifluro Acetic Acid Activated Carbon Hexane Valsartan L-Valine Methanol Thionyl Chloride Toluene DCM NaOH NaCL 4-Bromo Methyl 2-Cyano biphenyl Acetonitrile Potassium Carbonate 1.68 0.76 1.5 1.20 1.02 0.70 0.44 0.98 1.81 0.03 2.00 0.023 1.00 0.240 0.45 0.100 0.410 1.520 2.80 5.80 1.520 26.00 0.115 0.177 10.00 0.574 10.00 0.664 0.297 2.153 55.000 23.00 0.465 0.022 0.250 1.44 0.23 6.90 0.38 2.41 0.65 0.29 2.17 1.00 1.49 24. 25. 26. 27. Oxalic Acid o-Xylene Valeoryl Chloride Sodium Bicarbonate HCl Tributyl Tin Chloride Calcium Hydroxide Ethyl Acetate Diisopropyl ether TBAB Tranexamic Acid 4-aminomethyl benzoic Acid HCl Ruthenium Sodium hydroxide Methanol Folic Acid PABGA TAPS TCA SMBS NaHCO3 HCl 30% NaOH Acetic Acid Zolpidic Acid Toluene Methyl Phenacyl bromide 2- Amino-5-methyl pyridine Triethyl amine Oxalyl chloride Methylene Dichloride Potassium hydroxide Acetic acid Hydrazine hydrate Methanol Pregabaline Sodium Hydroxide 4-CMH Liquid Bromine Activated carbon Hyflo Hydrochloric acid IPA Morpholine Methyl-3-Amino Crotonate : 294 Kg. Mono Ethanol Amine 1.00 1.16 1.24 0.28 0.65 5.55 0.42 0.35 7.17 0.14 1.060 0.440 0.300 0.252 2.000 1.00 0.90 0.64 0.36 1.20 6.00 0.22 0.32 0.128 1.000 0.611 0.531 0.700 1.000 1.340 1.651 0.431 1.000 1.90 1.37 1.23 0.07 0.02 2.46 7.06 0.08 1.47 0.625 28. 29. 30. 31. Chlorohexidine Base Hexamethelinediamine Butanol Hydrochloric acid Sodiumdicynamide Parachloroaniline HCl Sodium hydroxide Methanol Benzarone Salicylaldehyde Chloroacetone Hydrazine hydrate KOH Methanol MEG Toluene p-Anisoyl chloride Ferric chloride Aluminium chloride HCl Activated carbon Ethyl Acetate Benzbromarone Salicylaldehyde Chloroacetone Hydrazine hydrate KOH Methanol MEG Toluene p-Anisoyl chloride Ferric chloride Aluminium chloride HCl Activated carbon Bromine TEA IPA Zaltoprofen 2-(2-(phenylthio)-5propionylphenyl)acetic acid Methanol Sulfuric Acid Sodium Carbonate Trimethyl Ortho Formate Zinc Dust Bromine 0.30 3.51 0.63 0.46 0.85 0.21 0.12 0.98 0.87 1.075 1.300 0.200 0.05 0.150 1.32 1.00 2.475 2.25 1.25 0.158 0.670 0.600 0.730 0.880 0.100 0.600 0.140 0.900 0.680 1.680 2.540 0.07 1.190 0.690 0.200 1.414 8.485 0.141 0.263 1.232 0.061 0.919 32. 33. 34. 35. 36. Sodium Hydroxide Toluene Polyphosphoric acid EDC Ethanol Acetic Acid Sodium Carbonate Ondansetron HCL Ondensetron Base IPA HCl Miconzole Nitrate 0.778 3.242 5.657 3.536 2.823 0.894 0.258 1,3-dichloro benzene Aluminum chloride Chloro Acetyl Chloride 2,2’,4’ Trichloro acetophenone 0.40 0.40 0.32 0.56 NaOH MeOH Sodium Borohydrate Imidazole Toluene 2,4-DBC Activated Charcoal Nitric Acid 0.10 0.08 0.04 0.17 0.16 0.46 0.008 0.24 Ecanzole Nitrate 1-(2,4-Dichloro phenyl)2-(1H-Imidazol-1yl)Ethanol Toluene NaOH 4-Chloro benzyl Chloride TBAB Nitric acid Methanol Desloratadine Loratidine Methanol KOH MIBK Loratidine M-5 Sulphuric Acid NaOH MDC SOCl2 DMF AlCl3 Hyflow Ethylene Dibromide THF 0.90 3.54 0.21 0.80 0.20 0.35 0.50 0.02 0.20 0.30 2.95 0.30 3.93 0.45 2.90 0.90 3.25 4.00 3.31 0.13 0.72 0.63 0.23 0.9 39 Iodine HCl Chloroform Hexane Toluene NaHCO3 Acetonitrile Gabapentine 1-1, Cycloacetic Acid Urea NaOH Xylene Conc. HCl Methanol Ethyl Acetate Albendazole Ortho Nitro Aniline Ammonium Thiocynate Methanol Chlorine Gas Caustic Soda N- Propanol N-Propyl Bromide Toluene Sodium Hydrosulphide Diluted Cyaanamide Solution (L-500) Methyl Chloro Format Acetone Citrizine HCL 40 P-Chloro benzophenone Methyl Alcohol Sodium Borohydrate Sodium Hydroxide Toluene Thionyl Chloride Hydroxy Ethyl Piperazine Sodium Hydroxide Lye Sodium Mono Chloro Acetate Dimethyl Formamide Potassium Hydroxide Acetone Activated carbon HCl gas Lasamide 37. 38 41 2,4 Dichloro Benzoic acid Chlorosulfonic acid Ammonia HCl MESALMINE POTASSIUM HYDROXIDE 0.005 1.50 1.50 2.20 1.50 1.75 0.20 1.67 1.00 0.62 0.58 2.34 0.30 0.30 1.06 1.24 0.20 0.76 0.91 0.383 0.90 0.380 4.50 0.52 0.65 0.18 1.00 1.35 0.07 0.01 0.25 0.85 0.80 2.00 0.38 0.15 0.65 0.20 0.02 0.20 0.950 4.720 0.720 1.296 2.54 2-chloro-5- nitro benzoic acid HYDROCHLORIC ACID SODIUM CARBONATE RANEY NICKEL SODIUM HYDROXIDE HYDROCHLORIC ACID CHARCOAL SODIUM BICARBONATE 42 FEBUXOSTAT Ethyl-2-(3-cyano-4-isobutoxyphenyl)-4-methyl5-thiazolecarboxylate Methanol Toluene Caustic soda flakes HCl 43 44 45 1.82 3.10 0.60 0.30 4.73 2.70 0.20 0.54 1.250 12.50 7.50 0.125 0.250 ITOPRIDE HYDROCHLORIDE Veratric acid Thionyl chloride Toluene 4-[2-(Dimethylamino) ethoxy]Benzyl amine Caustic soda flakes IPA IPA HCl Methanol Acetone Amrodafinil Benzhydrolthiol Chloroacetic Acid Sodium Hydroxide HCL (30%) Acetic Acid Hydrogen Peroxide L(-)Phenyl Ethyl Amine Methanol Ammonium Solution Carbon Hyflow QUETIAPINE FUMARATE 2- Amino diphenyle sulfide Sodium Hydroxide flakes Toluene Phenyl chloroformate Hydrochloric acid Polyphospheric acid Acetone Dibenzo [b,f] [1,4] Thiazepin -11(1 OH)- ONE N,N- Dimethyl ANILINE Phosphorous oxychloride Hydrochloric acid 0.667 0.667 3.270 0.667 0.095 2.857 0.317 0.159 0.635 2.90 1.37 0.58 0.20 6.62 0.88 0.30 0.14 0.52 0.12 0.12 1.11 0.32 6.67 1.27 0.66 8.89 3.48 0.6 0.4 0.3 0.5 Sodium Sulphate Toluene Triethanolamine Hydroxy ethoxyrthyl piparazine Sodium bicarbonate 1 N HCl Hyflosupercel Methanol Fumaric acid 46 ARIPIPERAZOLE 7- Hydroxy -3,4- dihydroQuinoline 1- Bromo -4- Chloro Butane Sodium Hydroxide n- Propanol Cyclohexane Triethylamine DCPP HCl Methanol 47 48 49 0.1 5.2 0.4 0.4 0.1 0.1 0.0 7.7 0.2 Amlodipine Besylate Phthaloyl Amlodipine Mono Methyl Amine Methanol Ethyl Acetate Benzene Sulfonic Acid Carbon NEBIVOLOL AND ITS INTERMEDIATE Maleic Anhydride AlCl3 EDC Para Fluoro Anisole HCl Hexane Acetic Acid Sulphuric Acid Pd/c Hyflow Sodium Borohydride THF MDC Sodium Carbonate DMSO Oxahl Chloride TEA Sodium Hydride Methanol Benzyl Amine Acetonitrile Sevelamer Hydrochloride Allylamine 2,2-Dimethyl-2,2-azopropane dihydrochloride HCl Epichlorhydrin 0.74 4.44 0.24 3.70 1.48 0.59 0.59 0.37 1.09 1.68 4.38 3.09 0.38 0.75 1.4 3.50 5.00 1.42 3.20 4.25 0.95 1.20 0.41 0.80 1.20 4.00 5.6 0.9 0.80 3.25 6.50 1.00 1.00 0.33 0.8 0.75 0.03 1.25 0.11 50 51 NaOH Flakes Sevelamer Carbonate SevelamerHCl Caustic soda flakes Carbon dioxide Poly Allaylamine Hydrochloride Allylamine 2,2-Dimethyl-2,2-azopropane dihydrochloride HCl 0.37 1.111 0.333 0.278 0.333 0.117 0.600 ANNEXURE-3 BRIEF MANUFACTRING PROCESS, CHEMICAL REACTION AND MASS BALANCE 1. Oxyclozanide Manufacturing Process: 3,5,6 Trichloro Salycylic acid, Thionyl chloride will be mixed with MCB and maintain for 2 hours at 75°-80°C. After TLC ok above mass will be filtered. Filtrate 2,4 Dichloro 6Amino Phenol will be mixed in solvent with MCB and will be maintain at 133°C temperature for 2 hours. After TLC ok adjustment of pH, above mass will be filtered and finish (crude) product will be obtained. Finish (crude), Acetone, Carbon, Hydrose will be mixed in water. Above mass will be filtered and dried to obtain finished product. Mass Balance: Water : 50 3,5,6 TC SA : 150 MC B : 3000 Thionyl Chloride : 75 REA CTION AT 80°C 40 HC L G A S SCRUBBE R HCl : 50 to ETL W ater : 100 Caus tic : 48 SO 2 G A S SCRUBBE R 30% N aHSO 3 : 188 3185 2,4 DCAP : 100 MCB : 3000 Sodium Bic arbonate :5 S OLV ENT RE COVERY Acetone : 12000 H ydrous : 10 S OLV ENT RE COVERY MC B Recovered : 5850 440 Acetone Recovered : 11725 725 W ashing water : 3500 F ILTRATI ON W astewater to CETP (ET L) : 4000 225 W ashing water : 800 W AS HI NG Wastewater to C ETP (ETL) : 900 125 D RY ING FINISHED P ROD UC T : O XYCLOZA NIDE : 10 0 K G . Evaporation Loss : 25 2. Furosemide Manufacturing Process: Lasamide, Furfuryl Amine, Sodium Bicarbonate will be added in Reactor and reaction will be carried out at 125°C for 4 hours. Caustic solution will be added to it and then Hydrochloric acid will be added to adjust the pH of the reaction mass. Then separate the org. residue and transfer remaining mass into another reactor for purification by adding carbon followed by filtration. Then chill the purified reaction mass to 0°- 5°C temp. Precipitation takes place and centrifuge the reaction mass followed by drying to obtain finished product. Mass Balance: Furfuryl Amine : 32 Lasamide : 90 Sodium carbonate : 25 Caustic Flakes : 10 SS R EACTOR 157 FILTRATION / SEPARATION Furfuryl Amine ML : 25 for Recovery Recovered Furfuryl Amine : 20 Kg. & Dist. Residue : 2.5 Kg. 132 DM Water : 200 Carbon : 1 P URIFICATION Spent Carbon to BEIL for Incineration : 1 332 CHILL UPTO 0°-5°C 332 CENTRI FUGE Wastewater to CETP (ETL) : 207 125 DRYING FINISHED P RODUCT : F UROSEMIDE : 100 KG. Note: Afore mentioned quantities are in Kg Evaporation Loss : 25 1. Diaminomethyleneamino(1-amino-1-iminomethylene) dihydrochloride [ITU] thiomethyl thiozole Manufacturing Process: Charge acetone into the reaction vessel. Chill acetone up to 10°C. Add slowly 1,3Dichloro acetone within 1 hour maintain temp. 10 °C. Add KI (Lot-1) at 10°C and stir the reaction mass for 15 minutes. Add Guanyl thiourea by maintaining temp. 12 °C to 15 °C. Add KI (Lot-2) at 15 °C to 20 °C and maintain for 3 hours. Add acetic acid (glacial) at 20°C to 25°C temp. Heat the reaction mass to 40 °C temp. Now add thiourea and acetone under stirring at 40 °C temp. Raise the temp. of the reaction mass to 55 °C to 60 °C. Reflux the reaction mass at 55 °C to 60°C temp. for 3 hours. Cool the reaction mass to 30 °C temp. Further cool to 20 °C temp. Centrifuge the material and wash the wet cake with acetone. Unload the wet cake from the centrifuge. Dry the wet cake in dryer at 95 °C to 100 °C temperature for 9 to 10 hours. Unload the dried material and weight and packed it. Chemical Reaction: q Mass Balance: Sr. No. 1 2 3 4 5 6 Total Input 1,3 DCA Guanyl Thiourea Acetone Catalyst Thiourea Acetic Acid Quantity (Kg) 0.435 0.413 3.100 0.004 0.261 0.261 4.474 Output Product Evaporation Loss Acetone Recover Dist. Residue Total Quantity (Kg) 1.000 0.400 3.000 0.074 4.474 2. N-Sulfomyl-3-chloropropionamide hydrochloride [IF] Manufacturing Process: Charge Acrylonitrile into the reaction vessel. Add hydrogen peroxide (50 %) under stirring. Chill the reaction mass to 15°C to 20°C. Purge HCl gas at 15°C to 20°C for 38 to 40 hours at the feeding rate of 0.8-1.0 Kg/hour. After completion of gas passing, degas the reaction mass. Now Add sulfamide under stirring at RT. Cool the reaction mass to 18°C to 22°C temp. Further chill the reaction mass to 0°C to 10°C temp. Purge HCl gas at 0°C to 10°C for 8 hours at the feeding rate of 0.8-1.0 Kg/hour. Raise the temp. of the reaction mass to 15°C to 20°C within 2 hours with continue HCl gas passing. Raise the temp. of the reaction mass to 50°C to 55°C within 2 to 3 hours with continue HCl gas passing. Maintain reaction mass at 50°C to 55°C for 5 hours with continue HCl gas passing. Degas the reaction mass for 5 hours at 50°C to 55°C temp. Cool the reaction mass to 28°C to 32°C temp. Further cool the reaction mass to 18°C to 22°C. Centrifuge the material and wash the wet cake with chilled acetone. Unload the wet cake and dry the wet cake in dryer at 65°C to 70°C temp. for 5 to 6 hours. Unload the dried material and record the weight and packed. Chemical Reaction: O H2C CH2CN + H2N NH2 O S NH2 Cl CH2 CH2 C N (1) (2) (1) Acrylonitrile (2) Sulfamide (3) N-sulfomyl-3-chloropropionamidehydrochloride (3) SO 2NH2 Mass Balance: Sr. No. 1 2 3 4 5 6 Total Input Acrylonitrile Hydrogen Peroxide HCl (Gas) Sulfamide Acetone Quantity (Kg) 1.303 0.008 1.495 0.500 0.400 3.706 Output Product Evaporation Loss Acetone Recover CAN Recover Dist. Residue Dil. HCl Total Quantity (Kg) 1.000 0.556 0.350 1.2907 0.050 0.46 3.706 3. Famotidine Manufacturing Process: STAGE-1: [FAMOTIDINE CRUDE]: Charge Methanol into the reaction vessel. Add caustic soda flakes and reflux the reaction mass under stirring. Cool to 30°C and then chill to 20°C to 22°C temp. Now add ITU (Diaminomethyleneamino(1-amino-1iminomethylene) thiomethyl thiozole dihydrochloride) and IF (N-Sulfomyl-3chloropropionamide hydrochloride) at 20°C to 22°C temp. Regulate the temperature to 25°C and maintain for 2 hours under stirring. Chill the reaction mass to 0°C to 5°C 22.temp. Centrifuge the slurry. Unload the wet material from the centrifuge. Charge water into the reaction vessel and add wet cake under stirring. Stir for 30 minutes. Centrifuge the material and wash the wet cake with water and then wash with methanol. Load the wet cake in dryer. Dry the wet cake at 80°C to 85°C temperature for 7 to 8 hours. Unload the dried material and weight it. STAGE-2: [FAMOTIDINE PURE]: Charge Water & caustic soda into the reaction vessel. Add Famotidine Crude (Stage-1) under stirring. Heat the reaction mass to 70°C to 75°C temperature. Check the clarity of the reaction mass. It should be clear. Now prepare the slurry of Activated carbon in water. Add activated carbon slurry into the reaction mass at 70°C to 75°C temp. And maint. for 15 minutes. Filter the reaction mass through pressure filter and transfer filtrate online to another reaction vessel maintaining temperature 30°C to 40°C. Add Acetic Acid & follow out the material Now chill the filtrate to 0°C to 5°C temp. and maintain for 30 minutes. Centrifuge the slurry and wash the wet cake with water. Unload the wet cake and weight it. Dry the wet cake in dryer at 75°C temperature for 5 to 6 hours. Unload the dried material and weight it and packed it as Famotidine Pure. Chemical Reaction: NH CH 2 S NH2 C N NH 2 H 2N + 2 HCl C l CH 2 CH 2 C N C SO 2 NH 2 NaOH N H 2N S (1) (2) NH 2 CH 2 S CH 2 N C C N H 2N H 2N CH 2 SO 2 NH 2 N S (3) (1) D iaminomethyleneamino(1-amino-1-iminomethylene)thiomethyl thiozole dihydrochloride (2) N -Sulfamyl-3-chloropro pionamidine hydrochloride (8) Famotidine Mass Balance: Sr. No. 1 2 3 4 5 6 Total Input ITU IF Methanol NaOH Water Acetic Acid Quantity (Kg) 1.150 0.965 5.710 0.690 20.50 0.200 29.215 Output Product Methanol Recover Methanol Loss Effluent Evaporation Loss Dist. Residue Total Quantity (Kg) 1.000 5.500 0.200 22.305 0.010 0.200 29.215 4. Sevelamer HCl Manufacturing Process: Stage-1 Preparation of Polyallylamine Hydrochloride Into clean reactor charge 250 Kg Hydrochloric acid at room temperature. Add 150 Kg allylamine in 2 hrs at 5 to 10 °C. Raise the temperature 80 °C and add a solution of 2,2dimethyl-2,2-azopropane dihydrochloride (6.0 Kg in 44 Kg water) at 45 to 50 °C. Stir the mass 30 hrs at 45 to 50 °C. Monitor the reaction performance by analytical methods. After completion of reaction, cool the mass to 25 to 30 °C Stir for 1 hr at 25 to 30 °C. Expected weight is 450 Kg. Stage-2 Preparation of Sevelamer Add 150 Kg Sodium hydroxide solution (75 Kg in 75 Kg water) into 450 Kg Polyallylamine at room temperature and stir for 30 minutes. add 22.0 Kg of epichlorohydrin into above solution at room temperature and stir for 20 minutes. Heat the mass at 25 to 50 °C in 10 to 20 minutes. Cool to 30 °C and stir for 30 minutes at 25 to 30 °C. Filter the slurry and wash the material and finally with 3 X 1500 Kg Water. Collect the main and washing Mother Liquor together. Unload and dry the material at 45 to 50 °C in vacuum tray drier (VTD) till to reach the required moisture content of the product. Expected weight is 200 Kg. Chemical Reaction: Stage –I (Preparation of Polyallylamine Hydrochloride): H2C allylamine NH2 + HCl Hydrochloric acid Polymerisation 25 to 80ºC Water . . .HCl NH2 n Polyallylamine Hydrochloride Stage – 2 (Preparation of Sevelamer): . .HCl . O NH2 Cl n + Polyallylamine Hydrochloride Hydroxide Cross Linking Na OH + Epichlorohydrin Sodium Water 25 to 50ºC CH3 H3C H2N.nHCl HN .nHCl a OH H2N .nHCl HN .nHCl H3C b Sevelamer a, b = number of primary amine groups c = number of cross linking groups n = fraction of protonated amines m = large number to indicate extended polymer network c m CH3 Mass Balance: Sr. Input No. 1 Allylamine 2 2,2-Dimethyl-2,2azopropane dihydrochloride 3 HCl 4 Water 5 Epichlorhydrin 6 NaOH Flakes Total Quantity (Kg) 150 6 250 2119 22 75 2622 Output Product Effluent Quantity (Kg) 200 2250 Evaporation Loss 172 Total 2622 4 (a). Sevelamer Carbonate Manufacturing Process: • Charge Purified Water and Sevelamer Hydrochloride. • Charge Caustic Soda flakes. • Purge Carbon Dioxide gas. • Filter the mass and wash with Water. • Dry wet material to give Sevelamer Carbonate. Chemical Reaction: Mass Balance: Sr. Input No. 1 SevelamerHCl 2 Caustic soda flakes 3 Carbon dioxide 4 Water Total Quantity (Kg) 1.111 0.333 0.278 37.778 39.500 Output Product Effluent Quantity (Kg) 1.000 35.556 Evaporation Loss 2.944 Total 39.500 5. Poly Allaylamine Hydrochloride Manufacturing Process: Into clean reactor charge 250 Kg Concentrated hydrochloric acid at room temperature. Add 150 Kg allylamine in 2 hrs at 5 to 10 °C. Raise the temperature 80 °C and add a solution of 2,2-dimethyl-2,2-azopropane dihydrochloride (6.0 Kg in 44 Kg water) at 45 to 50 °C. Stir the mass 30 hrs at 45 to 50 °C. Monitor the reaction performance by analytical methods. After completion of reaction, cool the mass to 25 to 30 °C Stir for 1 hr at 25 to 30 °C. Expected weight is 450 Kg. Chemical Reaction: H2C NH2 allylamine + HCl Hydrochloric acid Polymerisation 25 to 80ºC Water . .HCl . NH2 n Polyallylamine Hydrochloride Mass Balance: Sr. Input No. 1 Allylamine 2 2,2-Dimethyl-2,2azopropane dihydrochloride 3 HCl 4 Water Total Quantity (Kg) 150 6 250 44 450 Output Product Total Quantity (Kg) 450 450 6). Fomepizole Manufacturing Process Stage-1 Preparation of 1, 1-Diethoxy Propane Into reactor, charge 395 Kg Ethanol and 131 Kg Propanaldehyde at room temperature. Heat the mass to 90ºC and reflux for 15 hrs. Cool the mass to room temperature. Add 390 Kg Hexane and stir for 30 minutes at room temperature. Separate the layers. Distill out the Hexane completely at 80ºC. Expected weight is 300 Kg Stage-2 Preparation of Fomepizole Into the reactor charge 233 Kg N,N-Dimethyl formamide and 300 Kg 1,1- Diethoxy Propane at room temperature. Add 535 Kg Phosphorus oxychloride solution (345 Kg in 190 Kg N,N-Dimethyl formamide) into the mass in 14 hrs at 90ºC. Cool to 50ºC and stir for 12 hrs. Monitor the reaction performance by analytical methods. After completion of reaction cool the mass to room temperature. Into the mass add 2000 Kg Water and 2680 Kg Dichloro methane and stir for 30 minutes. Separate the layers and distill out Dichloro methane completely at below 50ºC. Into the above mass, add 2010 Kg Dichloro methane and 110 Kg Hydrazine hydrate at room temperature. temperature. Heat the mass to 100ºC reflux for 15 hrs at the reflux Monitor the reaction performance by analytical methods. After completion of reaction cool the mass to room temperature. Add 2000 Kg Water into the mass and adjust the pH to 7.0 using Potassium carbonate solution (75 Kg in 750 Kg Water). Separate the layers and wash the dichloro methane layer with 1000 Kg Water. Distill out Dichloro methane completely under vacuum at below 40ºC. Add 425 Kg Di isopropyl ether and stir for 30 minutes at room temperature. Add 15 Kg Carbon and stir for 30 to 40 minutes at room temperature. Filter and wash with 73 Kg Di isopropyl ether. Distill out Di isopropyl ether completely under vacuum at below 50ºC. Release the vacuum and unload the liquid Fomepizole. Chemical Reaction Stage – 1 (Preparation of 1,1-Diethoxy Propane) O H3C H3C OH H + Hexane / 90ºC H3C O O CH3 H3C Ethanol Propanaldehyde 1,1-Diethoxy Propane Stage-2 (Preparation of Fomepizole) H3C O O CH3 Cl Cl P H3C 1,1-Diethoxy Propane O Cl + Phosphorous Oxychloride + H2N NH2. H O 2 Hydrazine Hydrate N,N-Dimethyl Formamide (DMF) Dichloro Methane (MDC) Water 50ºC/ 90ºC 100ºC H N N H3C Fomepizole Mass Balance: Sr. Input No. Step-1 1 Propanaldehyde 2 Ethanol 3 Hexane 4 5 6 Total Quantity (Kg) Sr. Input No. Step-2 1 Step-I 2 Phosphorus oxychloride 3 Hydrazine Hydrate 4 Potassium Carbonate 5 Carbon 6 Di isopropyl Ether 7 N,N-Dimethyl Formamide 8 Dichloro Methane 9 Water 10 Quantity (Kg) Output Quantity (Kg) 300 Product 100 345 Dichloro methane 4670 110 75 15 498 Dichloro methane loss Dimethyl formamide Di isopropyl ether Di isopropyl ether loss 20 30 480 18 423 Carbon 15 4690 5750 Water Dimethyl formamide Dimethyl formamide loss Dist. Residue Total 11 Total 131 395 390 916 12206 Output Step-1 Ethanol Recover Ethanol Loss Hexane Recover Hexane Loss Dist. Residue Total Quantity (Kg) 300 378 15 375 15 2 916 6470 383 10 10 12206 7. COLESEVELAM Manufacturing Process Stage-1 Preparation of Polyallylamine Into clean reactor charge temperature. 301 Kg Concentrated hydrochloric acid at room Add 156 Kg Monoallylamine in 2 hrs at 5 to 10ºC. Raise the temperature and distill out water and excess hydrochloric acid under vacuum at below 60ºC. Add 95 Kg Water into the mass at room temperature. Raise the mass temperature to 45 to 50ºC and add a solution of 2,2-dimethyl-2,2-azopropane dihydrochloride (3 Kg in 10 Kg water) at 45 to 50ºC. Stir the mass 30 hrs at 45 to 50ºC. Monitor the reaction performance by analytical methods. After completion of reaction, cool the mass to 25 to 30ºC and transferred into 1354 Kg Methanol. Stir for 1 hr at 25 to 30ºC. Filter the slurry and wash the material with 395 Kg Methanol. Collect the main and washing Mother Liquor together. Unload and dry the material at 45 to 50ºC in vacuum tray drier (VTD) till to reach the required LOD (Loss On Drying) of the product. Expected weight is 245 Kg. Stage-2 Preparation of Colesevelam Add 200 Kg Sodium hydroxide solution (50 Kg in 150 Kg water) into 245 Kg Polyallylamine at room temperature and stir for 30 minutes. In a separate reactor, add 2 Kg of Epichlorohydrin, 4 Kg n-Decylchloride and 4 Kg Trimethyl ammonium hexylchloride into 63 Kg of above solution and at room temperature and stir for 20 minutes. Add this solution into the above remaining mass at 25 to 50ºC in 10 to 20 minutes. Cool to 30ºC and stir for 30 minutes at 25 to 30ºC. Filter the slurry and wash the material with 32 Kg Methanol, 100 Kg Water, 20 Kg Sodium hydroxide solution (1Kg in 19 Kg Water) and finally with 400 Kg Water. Collect the main and washing Mother Liquor together. Unload and dry the material at 45 to 50ºC in vacuum tray drier (VTD) till to reach the required moisture content of the product. Expected weight is 260 Kg. Chemical Reaction Stage – 1 (Preparation of Polyallylamine) NH2 H2C Monoallylamine Polymerisation + HCl Hydrochloric acid 45 to 50ºC Water . . .HCl NH2 n Polyallylamine Hydrochloride Stage-2 (Preparation of Colsevelam HCl) . .HCl . NH2 n + NaOH + Polyallylamine Hydrochloride rochloride O H3C Cl + Epichlorohydrin + n-Decyl chloride CH3 + N Cl H3C Trimethylammoniumhexylchloride Cross Linking 25 to 50ºC CH3 H2C NH N H3C H2C + CH3 NH CH3 O H2C NH2 Cl .HCl n Colesevelam Hydrochloride Mass Balance: Sr. Input No. Step-1 1 Monoallylamine 2 2,2-dimethyl-2,2azopropane dihydrochloride 3 Concentrated Hydrochloric acid 4 Methanol 5 Water Total Quantity (Kg) Sr. Input No. Step-2 1 Polyallylamine 2 Epichlorohydrin 3 n-Decylchloride 4 Trimethylammoniumh exylchloride 5 Sodium hydroxide 6 Methanol 7 Water Total Quantity (Kg) 156 Output Step-1 Methanol Recover Quantity (Kg) 245 1696 3 301 1749 105 2314 245 2 4 4 116 32 849 1252 Methanol Loss 52 Effluent 321 Total 2314 Output Quantity (Kg) Product Efflunet Sodium chloride Methanol 260 788 172 32 Total 1252 9. Glimepiride Manufacturing Process • Charged 3 Ethyl 4 methyl Pyrroline and toluene is SSR. Charged slowly 2 Phenyl Isocyante in it. Heat the RM to reflux for 2 hrs. • Cool and then chilled the rm. Filter the mass and dry it. • Charged Chloro Sulfonic Acid in Reactor at RT and chilled it. Charged Amide derivative in above reaction mixture in chilling condition. • The reaction mixture was heated and stirred. The reaction mixture was very slowly quenched in chilled ammonia solution. Filter the solid mass, wash with water and dry it. • Charged EDC and above crude product in Reactor at RT. The reaction mixture was heated and stirred the chilled to 0-5oC. Filter the solid mass under chilling condition and dry it. Chemical Reaction: Mass Balance: Sr. Input No. 1 3 Ethyl methyl Pyrroline 2 2 Phenyl ethyl isocyanate 3 Toluene 4 Chloro Sulfonic Acid 5 Ammonia Solution 6 EDC 7 Water Total Quantity (Kg) 0.40 Output Quantity (Kg) Product 1.00 0.40 Toluene Recover 3.35 3.50 EDC Recover Distillation + Drying loss Residue Effluent 1.70 1.00 3.10 2.00 1.00 11.29 Total 0.83 0.03 4.38 11.29 10. Furosemide Manufacturing Process: To Furfurylamine, 2,4-Dichloro-5-Sulfamoyl Benzoic acid (Lasamide) will be added below 60°C. Gradually, temperature of the reaction mixture, under Nitrogen atmosphere will be raised to 117- 120°C and maintained for several hrs. The reaction mass will be cooled and passing of Nitrogen gas will be stopped and diluted with Isopropyl Alcohol. Subsequently the pH of reaction mass will be adjusted to highly alkaline with solution of sodium hydroxide & cooled to 0°C for several hours. When the crude sodium Frusemide separates out, it will be centrifuged. The sodium salt of Frusemide will be dissolved in DM water, charcolised and filtered. pH of clear solution will be adjusted to acidic when pure Frusemide separates out. It will be centrifuged, washed with DM water & dried. Dried product will be milled blended, shifted and packed. Chemical Reaction: Mass Balance: Sr. Input No. 1 Furfuryl Amine 2 Lasamide 3 Caustic Flake 4 IPA 5 Carbon 6 Water 7 Acetic Acid 8 Total Quantity (Kg) 1564 850 234 5920 80 7396 220 16263 Output Product Furfuryl Amine Recover Loss Dist. Residue Spent Carbon Effluent IPA Recover IPA Loss Total Quantity (Kg) 1000 1210 450 20 70 7593 5680 240 16263 11. BETAHISTINE DIHYDROCLORIDE: Manufacturing process: 2-vinyl pyridine react with methylamine hydrochloride in presence of acetic acid to form betahistidine Base isolated by high vacuum distillation. Betahistidine Base react with IPA Hcl to form Betahistidine dihydrochloride. CHEMICAL REACTION: N + H3C CH3 NH2 HCl CH3 N NH Molecular Formula: C7H9N Molecular Formula: CH6ClN Formula Weight: 107.15306 Formula Weight: 67.51804 CH3 N Molecular Formula: C8H12N2 Formula Weight: 136.19428 2 HCl IPA HCl NH CH3 N NH Molecular Formula: C8H12N2 Formula Weight: 136.19428 Molecular Formula: C8H14Cl2N2 Formula Weight: 209 Mass Balance: Sr. Input No. 1 2 3 4 5 6 7 8 Total 2- vinyl pyridine Methylamine hydrochloride water Chloroform Sodium hydroxide Acetic Acid IPA IPA HCl(20%) Quantity (Kg) 0.63 0.80 0.31 3.13 0.45 0.06 2.50 1.38 9.25 Output Quantity (Kg) Product Effluent Chloroform Recovery Chloroform Loss IPA Recovery IPA Loss Distillation residue 1.00 2.22 2.90 0.23 2.40 0.10 0.40 Total 9.25 12. Adapalene Manufacturing Process: Charge THF & start nitrogen purging until water quenching. Charge Mg turnings. Heat the mass up to reflux 60-65°C . Prepare solution of adamentanol & p- bromomphenol in MDC inn a clean container. Add above prepared solution through the addition funnel in 10 – 15 min at 60-65°C. Prepare solution of Adamentanol in MDC in clean container. Add above prepared solution of in THF in 45-60 min at 60-65°C. Reflux the reaction mass for 60 min. Cool the reaction mass. Charge MDC to the reaction mass. Cool the reaction mass. Charge 6-Bromo-2-methyl naphthoate at 15-20°C. Maintain the reaction mass for 30 min at 40- 45°C. Take purified water in RBF & cool it 20-25. Prepare HCl water solution Add the HCl water solution slowly. Stir the reaction mass. Wash with purified water. Suck dry well. Unload the material of crude stage C wet cake & take for purification. Dry the wet cake at 70 – 75°C. Chemical Reaction: Step-2 Step-3 Step-4 Mass Balance: Sr. Input No. 1 2 3 4 5 6 7 8 Total Adamentanol Para Bromo Phenol THF Mg Turning MDC 6-Bromo-2-methyl naphthoate HCl Water Quantity (Kg) 24 15 30 3 68 36 66 350 592 Output Product Effluent MDC Recovery MDC Loss THF Recovery THF Loss Distillation residue Total Quantity (Kg) 50 442.5 65 2 29 0.5 3 592 13. TELMISARTAN AND ITS INTERMEDIATE Manufacturing Process: 4-Amino-3-benzoic acid is esterifies to gives methyl-4-amino-3-bezoate, which reacted with butryl chloride to produce butyramide derivative, which nitrated with fuming nitric acid to produced nitro derivative, which reduced in presence of Palladium on charcoal and then hydrolyzed to gives Benzimidazole derivative. Benzimidazole is reacted with n-methyl o-pheniline Diamine to gives condensed product, which is reacted with bromo ester to gives telmi ester, which hydrolyzed with potassium hydroxide to gives Telmisartan. Chemical Reaction: CH3 CH3 NH2 NH2 CH3OH/H2SO4 HO H3C O 65°C O O M wt - 165 TS-1 TS-1 Yield 94 % O O CH3 CH3 O NH2 H3C NH H3C O Cl H3C O TEA/MDC 0 to 5°C Yield 96 % O O M wt - 235 TS-2 O CH3 O NH Fuming HNO3 CH3 NH H3C CH3 O -20 to -25°C Yield 93 % H3C O CH3 NO2 O M wt - 280 TS-3 O NH O CH3 O CH3 H3C CH3 CH3 Pd/Charcoal Acetic Acid H3C H N O N 80°C NO2 CH3 O O M wt - 232 TS-5 CH3 CH3 H N 10% NaOH Sol. H H N O CH3 N H3C O N CH3 Methanol O Yield 86 % M wt - 218 TS-6 O Polyphospheric Acid CH3 H N 140 to 145°C CH3 CH3 H N N N H O N N CH3 NH2 O NH CH3 Yield 96 % M wt - 304 TS-7 CH3 Mass Balance: Qty (Kg) INPUT Raw material 3.53 1.484 Methanol 4-Amino 3-Methylbenzoic acid 1.423 Conc. Sulphuric acid 2.968 Liq. NH3 9.410 Total OUTPUT Material Qty(Kg) TS-01 ML to ETP 7.574 Output Loss Qty (Kg) 1.53 5.670 INPUT Raw material TS-1 MDC OUTPUT Material Qty(Kg) TS-02 Soduim Sulpahte Aqs. Layer 1.314 1.287 0.153 0.387 12.240 5.094 TEA Butryl chloride Sodium Bicarbonate Sodium Sulphate Water Hexane Recovered MDC+Hexane ML to ETP 27.675 Total Output 0.387 12.240 6.084 7.705 Loss Qty (Kg) 0.90 4.050 0.090 9.000 14.040 INPUT Raw material TS-2 Fuming Nitric acid Sodium Bicarbonate DM Water Total 1.53 0.31 OUTPUT Material 0.90 0.359 Qty(Kg) TS-03 ML to ETP 12.748 Output Loss 1.00 0.292 14) Tapentadol Hydrochloride Manufacturing Process: • Charge isopropyl alcohol, 3-methoxy propiophenone, dimethyl amine hydrochloride, Paraformaldehyde. Heat the reaction mass. Maintain the reaction mass and distill out isopropyl alcohol. Charge Purified water and sodium hydroxide. • Charge dichloromethane and separate out layers. Charge dichloromethane layer into the reactor and distill out dichloromethane. Charge IPA and charge L (-) Dibenzoyl tartaric acid. Maintain the reaction mass and filter it. Charge Purified water and above wet cake. • Charge sodium carbonate and Dichloromethane. Separate out layers. Charge dichloromethane layer into the reactor and distill out dichloromethane and charge Tetrahydrofuran. Charge magnesium turning and ethyl acetate. Maintain the reaction mass and distill out Tetrahydrofuran. Charge Purified water and Acetic acid. Add ammonium solution and Dichloromethane. Stir the reaction mass and separate out layers. Charge Product layer into a reactor and distill out dichloromethane. Charge Ethyl acetate into the above reactor and cool the reaction mass. Charge Trifluoroacetic anhydride and maintain the reaction mass. Unload the reaction mass. • Charge palladium and apply hydrogen pressure. Maintain the reaction mass. Filter the reaction mass and collect filtrate. Charge hydrobromic acid into the reaction mass. Heat the reaction mass and maintain the reaction mass charge ammonia solution and ethyl acetate. Separate out layers. Distill out ethyl acetate and charge Isopropyl alcohol. Add IPA HCl. Maintain the reaction mass. Centrifuge the reaction mass.Dry it to give Tapentadol Hydrochloride. Chemical Reaction: Mass Balance: Sr. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Total Input 3-methoxy propiophenone IPA Dimethyl Amine HCL Paraformadehyde Sodium Hydroxide MDC L (-) Dibenzoyl tartaric acid THF Mg Turning Ethyl Bromide Acetic Acid Ammonium Solution Ethyl Acetate Trifluroacetic anhydride Palladium Acetone HBr IPA HCl Water Quantity (Kg) 1.412 7.530 1.059 0.588 0.376 10.00 1.412 3.530 0.171 0.588 0.118 0.506 5.883 0.882 0.070 6.470 1.765 0.882 17.647 60.889 Output Quantity (Kg) Product IPA Recover IPA Loss MDC Recover MDC Loss THF Recover THF Loss Ethyl Acetate Rec. Ethyl Acetate Loss Palladium Recover Palladium Loss Acetone Recover Acetone Loss Effluent Dist. Residue Process Waste Loss 1.00 7.15 0.35 9.60 0.35 3.42 0.08 5.65 0.23 0.06 0.01 6.21 0.26 25.827 0.407 0.235 0.05 Total 60.889 15. Colistimethate Sodium Manufacturing Process: Stage 1: Take Colistin sulphate and water. Filter and remove insoluble material. Charge sodium bi carbonate solution. Add sodium carbonate for adjusting pH. Get white precipitation. Add 400 ml sodium bi carbonates solution. Add dematerialized water and adjust pH by adding sodium carbonate. Continue stirring 2 hours. Filter the reaction mass under nitrogen gas. Unloaded wet cake and charge dematerialized water. Add slowly sodium bi sulfite solution for adjust pH. Maintain 1 hour. Add remaining solution in reaction mass for pH. Stirring for 2 hours. Add acetic acid. Adjust pH. Stir for 1 hour. Add industrial solvent. Start a zeotropic distillation. Strip out 2 times from industrial solvents. Thick slurry mass is obtained. Add acetone for make free flowing slurry. Maintain 6 hours. Filter and unload wet cake. Dry under vacuum. Final Stage: Take crude stage-1 and methanol, add industrial solvent. Filter with flow bed. Wash with methanol. Distill out methanol under vacuum. Add Industrial solvent under stirring and get uniform slurry. Distill out methanol under vacuum. After complete distillation, add industrial solvent and maintain for 2 hours at 25 to 30oC temperature. Filter and wash with Industrial solvent. Dry under vacuum at 25 to 30 oC temperature for 4 hours. After drying continue 6 hours on 45 to 60oC temperature. Getting final material. Chemical Reaction: Mass Balance: Sr. No. Step-I 1 2 3 4 5 6 7 8 9 Total Step-II 9 10 11 12 13 Total Input Colistin Sulphate Sodium Bicarbonate Sodium Carbonate Formaldehyde Sodium Bisulfite Acetic Acid Solvent Acetone Water Step-I Methanol Water Quantity (Kg) Output Quantity (Kg) 100 50 25 100 230 12 2100 3400 3000 9017 Step-I Solvent Recover Solvent Loss Acetone Recover Acetone Loss Dist. Residue Effluent Drying Loss 155 2015 85 3230 170 50 3227 85 Total 9017 155 5800 1340 Product Methanol Recover Methanol Loss Effluent Solid Waste Total 75 5510 250 1430 30 7295 7295 16. Chlorohexidine Base Manufacturing process: First charge the Hexamethelinediamine and butanol then added concentrated hydrochloric acid and sodiumdicyamide into the reactor Heat the mass and distill out water then reflux at desire temperature, cool and charged parachloroaniline and reflux. Charge Sodium hydroxide flaks and water then separated the layers, Chilled the Organic phase and centrifuge. Wet material further subjected to purification in methanol, chill, and centrifuge followed by washing with methanol and dried it. CHEMICAL REACTION: NH2 H2N Hexametheline diamine + 2 HCl Hydrochloric acid M.W.116.2 M.F. C6H16N2 M.W.36.5 M.F. HCl [1 Eq.] [2 Eq.] NH2.HCl HCl. H2N Hexametheline diamine dihydrochloride M.W.189.2 M.F. C6H18N2Cl2 [1 Eq.] N NH2 HCl + HCl H2N Hexametheline diamine dihydrochloride 2 Na N N M.W.189.2 M.F. C6H18N2Cl2 Sodiumdicynamide M.W.89.03 M.F. C2N3Na [1 Eq.] [2 Eq.] N HN HN NH NH NH NH 1,1'-hexane-1,6-diylbis(3-cyanoguanidine) [1Eq.] 2 NaCl Sodium chloride N M.W.250.3 M.F. C10H18N8 + M.W.58.2 M.F. NaCl [2Eq.] NH2 N HN HN NH + NH NH Cl NH N Parachloroaniline Hydrochloride 1,1'-hexane-1,6-diylbis(3-cyanoguanidine) M.W.164 M.W.250.3 M.F.C10H18N8 M.F.C6H7NCl2 [2Eq] [1Eq] Cl HCl 2 NH NH NH NH NH NH NH NH . 2HCl NH Chlorhexidine dihydrochloride NH Cl M.W.578.4 2NaOH Sodium hydroxide M.F.C22H32Cl4N10 [1Eq] M.W.40 [2Eq] Cl NH NH NH NH NH NH NH NH NH Chlorhexidine Base NH Cl M.W.505.4 M.F.C22H30Cl2N10 [1Eq] + + 2H2O water 2NaCl Sodium chloride M.W.18 M.W.58.5 [2Eq] [2Eq] MASS BALANCE: Sr. No. Input 1 2 3 4 5 6 7 Hexamethelinediamine Butanol Hydrochloric acid Sodiumdicynamide Parachloroaniline HCl Sodium hydroxide 8 Methanol Total Water Quantity (Kg) 100 1170 210 153.40 283.30 70 870 830 3686.7 Output Effluent Residue Butanol Recover Butanol Loss Methanol Methanol Loss Chlorhexidine base Total Quantity (Kg) 1250 103.70 1117 53 793 37 333 3686.7 17. Benzarone Manufacturing Process: Stage-1: [BZN-A] Charge Methanol, Potassium hydroxide and Salicylaldehyde into the reactor. Apply steam to achieve temperature 70°C. Maintain and reflux for 30 minutes. Cool the reaction mass to 28°C to 32°C. Chill the reaction mass to 15°C to 20°C. Start addition of Chloroacetone and maintain temperature 15°C to 20°C. Apply steam in the jacket of reactor to achieve temperature 80°C. Reflux for 3 hours at 80°C. Cool the reaction mass to achieve temperature 50°C. Filter the material & separate the potassium chloride cake & ML. Wash the cake with Methanol. Transfer the filtrate material to reactor. Apply steam and distil out Methanol till 80°C. Cool the reaction mass to achieve the temp. 40°C. Charge Monoethylene glycol in reactor through vacuum. Charge Hydrazine hydrate (80%) through vacuum. Apply steam to achieve the temperature 120°C. Cool the reaction mass to achieve temperature 30°C to 35°C. Start addition of Potassium hydroxide at 30°C to 40°C. Apply steam to achieve the temp. 120°C. Maintain and reflux for 3 hours. After reflux stop applying steam and cool the reaction mass to achieve the temperature 100°C. Apply steam in the bottom of reactor and start steam distillation. Distillate & Separate Aqueous layer / Organic layer in HDPE tank. Transfer the organic material from HDPE tank to HDPE container as finished product BZN-A. Stage-2: [BZN-B] Charge Toluene in reactor. Charge BZN-A. Apply steam and start distillation to remove water from the reaction mass azeotropically till 115-118 °C. Cool the reaction mass to achieve room temperature. Charge p-Anisoyl chloride. Chill the reaction mass to achieve temperature 0°C to –5°C. Add slowly Ferric chloride between 0°C to 5°C in 3.0 – 5.0 hours. Stir and maintain 0 to 5°C for 30 minutes. Cool the reaction mass to 25°C to 30°C. Stir and maintain temperature 25°C to 30°C for 5 hours. Cool the reaction mass to 0°C – 5°C. Charge Water with maintaining temperature between 0°C-10°C. Stir the reaction mass for 30 minutes at 0°C - 5°C. Cool to 25°C – 30°C. Filter the material. Collect the filtrate in HDPE tank. Wash the cake with Toluene. Charge filtrate material into reactor and stir for 30 minutes. Settle for 30 minutes. Separate Aqueous layer & Organic layer in separate HDPE tank respectively. Charge Aqueous layer and Toluene into reactor. Stir for 30 minutes. Settle for 30 minutes. Charge organic layer into reactor. Charge Hydrochloric acid. Stir for 30 minutes. Settle for 30 minutes. Collect Aqueous layer in HDPE tank. Charge Hydrochloric acid. Stir for 30 minutes. Settle for 30 minutes. Collect Aqueous layer in HDPE tank. Start distillation upto 115°C-118°C & distil out toluene. Cool the reaction mass to achieve 25°C-30°C. Charge Aluminium chloride under stirring. Raise the temp. to 50°C - 55°C. Stir and maintain reaction mass for 5 hours at 50°C - 55°C. Cool the reaction mass to 30°C. Quench the mass in previously ready 20 slab ice + Hydrochloric acid. Keep temperature below 5°C during quenching. Stir for 1 hour at 0 to 5° C for complete solidification of material. Centrifuge the Material at 0°C to 5°C and wash the cake with chilled water (0-10°C) till pH of ML is 3 to 4. Weigh the wet cake. Charge Toluene in reactor. Charge wet cake in reactor under stirring. Apply steam to achieve temperature 100°C to get clear solution. Start azeotropic distillation. Take Toluene in HDPE tank and add Activated carbon [B] and stir it manually with SS rod to make slurry. Charge Activated carbon slurry into the reaction mass. Stir for 30 minutes at 100°C. Filter the reaction mass through pressure filter. Charge the filtered mater ial in reactor. Chill the filtered material to 5°C. Stir and maintain the temperature for 1 hour at 0°C-5°C. Centrifuge the chilled mass and wash the cake with chilled Toluene. Weigh the wet cake. Load the wet material in dryer and dry the material at 60°-70°C for 4 hours. Unload the dried material and pack as BZN-B. Stage-3: [BZN-P] Charge Ethyl acetate in reactor. Charge BZN-B in reactor. Raise the temperature of the reaction mass to 75°C to 80°C for 30 minutes. Cool the reaction mass to 20°C to 25°C. Stop cooling and chilled the reaction mass to 0°C to 5°C. Maintain the temperature 0°C to 5°C for 1.0 hour. Centrifuge the material. Weigh the wet cake. Charge Ethyl acetate in reactor. Add wet cake in reactor under constant stirring. Heat the reaction mass up to 750C - 800C. Add slurry of Activated carbon [B] in Ethyl acetate in reactor. Reflux the reaction mass for 30 minutes at 750C to 800C. Filter reaction mass through pressure filter. Transfer the filtrate on line to the reactor. Heat the filtrate at 75°C80°C. Distil out Ethyl acetate (70% of total quantity of Ethyl acetate used) from reaction mass at 75°C- 80°C. Cool the reaction mass to 30°C ± 2°C. Further, cool the reaction mass to 20°C ± 2°C. Chill the reaction mass to 0°C ± 5°C. Maintain the reaction mass at 0°C ± 5°C for 1.00 hour. Centrifuge the Material. Wash the cake with Ethyl acetate. Weigh the wet cake and record the gross weight, tare weight and total weight. Ensure cleanliness and dryness status of Dryer. Dry the wet cake in dryer at 65°C ± 2°C. Unload the dry material and pack as BENZARONE. Chemical Reaction: Mass Balance: Sr. Step-I 1 2 3 4 5 6 7 8 Total Step-II 1 2 3 4 5 6 7 8 9 Total Step-III 1 2 3 4 Total Input Salicylaldehyde Chloroacetone Hydrazine hydrate KOH Methanol MEG Quantity (Kg) 0.980 0.870 1.075 1.300 3.100 2.150 Step-II Ethyl Acetate Activated Carbon Quantity (Kg) Step-I Methanol Methanol Loss MEG recover MEG Loss Dist. Residue Effluent 1.100 2.900 0.200 2.100 0.050 0.020 1.930 KCl Cake Total 1.175 9.475 1.100 5.650 1.320 1.000 2.475 2.250 1.250 10.00 1.600 26.645 Step-II Toluene Recover Toluene Loss Dist. Residue Spent Carbon Solid Waste Effluent Loss 1.330 5.300 0.15 0.015 0.100 0.050 19.05 0.665 Total 26.645 1.330 3.170 0.100 Product Ethyl Acetate Ethyl Acetate Loss Spent Carbon Total 1.000 3.011 0.158 0.100 4.600 9.475 Step-I Toluene p-Anisoyl chloride Ferric chloride Aluminium chloride HCl Activated carbon Ice Water Output 4.600 18. BENZBROMARONE Manufacturing Process (a) Manufacturing Process: Stage-1: [BZB-1] Charge Methanol, Potassium hydroxide and Salicylaldehyde into the reactor. Apply steam to achieve temperature 70°C. Maintain and reflux for 30 minutes. Cool the reaction mass to 28°C to 32°C. Chill the reaction mass to 15°C to 20°C. Start addition of Chloroacetone and maintain temperature 15°C to 20°C. Apply steam in the jacket of reactor to achieve temperature 80°C. Reflux for 3 hours at 80°C. Cool the reaction mass to achieve temperature 50°C. Filter the material & separate the potassium chloride cake & ML. Wash the cake with Methanol. Transfer the filtrate material to reactor. Apply steam and distil out Methanol till 80°C. Cool the reaction mass to achieve the temp. 40°C. Charge Monoethylene glycol in reactor through vacuum. Charge Hydrazine hydrate (80%) through vacuum. Apply steam to achieve the temperature 120°C. Cool the reaction mass to achieve temperature 30°C to 35°C. Start addition of Potassium hydroxide at 30°C to 40°C. Apply steam to achieve the temp. 120°C. Maintain and reflux for 3 hours. After reflux stop applying steam and cool the reaction mass to achieve the temperature 100°C. Apply steam in the bottom of reactor and start steam distillation. Distillate & Separate Aqueous layer / Organic layer in HDPE tank. Transfer the organic material from HDPE tank to HDPE container as finished product BZB-1. Stage-2: [BZB-2] Charge Toluene in reactor. Charge BZB-1. Apply steam and start distillation to remove water from the reaction mass azeotropically till 115-118 °C. Cool the reaction mass to achieve room temperature. Charge p-Anisoyl chloride. Chill the reaction mass to achieve temperature 0°C to –5°C. Add slowly Ferric chloride between 0°C to 5°C in 3.0 – 5.0 hours. Stir and maintain 0 to 5°C for 30 minutes. Cool the reaction mass to 25°C to 30°C. Stir and maintain temperature 25°C to 30°C for 5 hours. Cool the reaction mass to 0°C – 5°C. Charge Water with maintaining temperature between 0°C-10°C. Stir the reaction mass for 30 minutes at 0°C - 5°C. Cool to 25°C – 30°C. Filter the material. Collect the filtrate in HDPE tank. Wash the cake with Toluene. Charge filtrate material into reactor and stir for 30 minutes. Settle for 30 minutes. Separate Aqueous layer & Organic layer in separate HDPE tank respectively. Charge Aqueous layer and Toluene into reactor. Stir for 30 minutes. Settle for 30 minutes. Charge organic layer into reactor. Charge Hydrochloric acid. Stir for 30 minutes. Settle for 30 minutes. Collect Aqueous layer in HDPE tank. Charge Hydrochloric acid. Stir for 30 minutes. Settle for 30 minutes. Collect Aqueous layer in HDPE tank. Start distillation upto 115°C-118°C & distil out toluene. Cool the reaction mass to achieve 25°C-30°C. Charge Aluminium chloride under stirring. Raise the temp. to 50°C - 55°C. Stir and maintain reaction mass for 5 hours at 50°C - 55°C. Cool the reaction mass to 30°C. Quench the mass in previously ready 20 slab ice + Hydrochloric acid. Keep temperature below 5°C during quenching. Stir for 1 hour at 0 to 5° C for complete solidification of material. Centrifuge the Material at 0°C to 5°C and wash the cake with chilled water (0-10°C) till pH of ML is 3 to 4. Weigh the wet cake. Charge Toluene in reactor. Charge wet cake in reactor under stirring. Apply steam to achieve temperature 100°C to get clear solution. Start azeotropic distillation. Take Toluene in HDPE tank and add Activated carbon [B] and stir it manually with SS rod to make slurry. Charge Activated carbon slurry into the reaction mass. Stir for 30 minutes at 100°C. Filter the reaction mass through pressure filter. Charge the filtered material in reactor. Chill the filtered material to 5°C. Stir and maintain the temperature for 1 hour at 0°C-5°C. Centrifuge the chilled mass and wash the cake with chilled Toluene. Weigh the wet cake. Load the wet material in dryer and dry the material at 60°-70°C for 4 hours. Unload the dried material and pack as BZB-2. Chemical Reaction: Stage-3: [BZB-3] Charge Methanol (Lot-I) in reactor. Chill the Methanol up to 0°C – 5°C. Add Bromine under constant agitation, and maintain the solution at 0°C – 5°C. Charge Methanol (Lot-II) inanother reactor and Stir it for 15 minutes. Add BZB-2 under constant stirring. Agitate thereaction mass to get clear solution. Add Triethylamine in the reaction mass at 25°C. Cool the reaction mass up to 18°C ± 2°C. Chill the reaction mass up to 0°C 5°C. Add dilute solution of Bromine from first reactor at 0°C-5°C within 10.0 to 15.0 hrs. Slowly heat the reaction mass up to 20°C to 25°C and maintain for 4.0 hours. Centrifuge the Material and wash wet cake with Methanol (Lot-III). Unload the wet material from the Centrifuge. Charge Water in Reactor and add above wet cake under stirring at room temperature. Centrifuge the Material and wash wet cake with Methanol (Lot-IV). Dry the wet cake in dryer at 60°C to 70°C temperature for 8.0 to 10.0 hrs. Weigh the dry material and affix the label as BZB-3. Stage-4: [BZB] Charge Isopropanol (Lot-I) in SS Reactor. Add BZB-3 under constant stirring. Stir reaction mass for 30 minutes. Heat the reaction mass up to 800C - 820C. Reflux the reaction mass for one Hour at 800C - 820C. Add slurry of Activated carbon [A] in reaction mass at 80°C – 82°C. [Prepare the Slurry of Activated carbon [A] in 25 L of Isopropanol (Lot-II)] Stir reaction mass for 30 minutes. Filter the reaction mass from SS Reactor and transfer the filtrate into the Glass lined reactor. Slowly cool the filtrate to 30°C ± 2°C and then further cool to 20°C ± 2°C. Centrifuge the Material and wash wet cake with Isopropanol (Lot-IV). Dry the wet cake in dryer at 55°C to 60°C temperature for 5 to 6 hours. Weigh the dry product, affix the label as BENZBROMARONE. Mass Balance: Sr. Step-I 1 2 3 4 5 6 7 8 Total Step-II 1 2 3 4 5 6 7 8 Total Step-III 1 2 3 4 5 Total Step-IV 1 2 3 4 Total Input Salicylaldehyde Chloroacetone Hydrazine hydrate KOH Methanol MEG Quantity (Kg) 0.670 0.600 0.730 0.880 2.100 1.460 Output Quantity (Kg) Step-I Methanol Methanol Loss MEG recover MEG Loss Dist. Residue Effluent 0.750 2.000 0.100 1.400 0.060 0.010 1.230 6.440 KCl Cake Total 0.800 6.440 Step-I Toluene p-Anisoyl chloride Ferric chloride Aluminium chloride HCl Activated carbon Water 0.750 6.140 0.900 0.680 1.680 2.540 0.070 8.10 20.860 Step-II Toluene Recover Toluene Loss Dist. Residue Spent Carbon Solid Waste Effluent Loss Total 0.900 6.000 0.140 0.010 0.060 0.030 13.220 0.500 20.860 Step-II Methanol Bromine TEA Water 0.900 4.000 1.190 0.690 4.500 11.280 Step-III Methanol Recover Methanol Loss Effluent Loss Total 1.200 3.800 0.200 4.97 1.110 11.280 Step-III IPA Activated Carbon 1.200 5.300 0.120 Product IPA Recover IPA Loss Spent Carbon Total 1.000 5.100 0.200 0.320 6.620 6.620 19. Carvedilol Manufacturing process Guiacol is condensed with Ethylene Dichloride to give 2-(2-Methoxyphenoxy)ethyl Chloride(CV-1). CV-1 is reacted with Pthalimide to give 2-(2-methoxyphenoxy) ethyl phthalimide (CV-2). Dephthaloylation and treatment with HCl gives 2-(2methoxyphenoxy) ethyl amine hydrochloride(CV-3 HCl) , which is further basified to give 2-(2-methoxyphenoxy)ethyl Amine (CV-3). Simultaneously 1,3 Cyclohexandione is reacted with phenyl hydrazine to give 1,3 cyclohexandione mono phenyl hydrazone (CV-4). CV-4 was cyclized under acidic conditions to give 1,2,3,4-tetrahydrocarbazol-4-one(CV-5). Catalytic aromatization of CV-5 gives 4-hydroxy-9-(H) carbazole (CV-6). CV-6 is further reacted with Epichlorohydrin to give 4-oxyranylmethoxy-9-(H)-carbazole(CV-7). CV-7 and CV-3 are then reacted together to give crude CV-8. It is then purified to get Carvedilol. Chemical Reaction: Synthetic Route of Carvedilol O O N H CV 7 O Dioxane NH 2 OCH 3 CV 3 Toluene:Cyclohexane:Ethyl acetate (60:19:21) OH O O NH H 3 CO N H Carvedilol (CV ) Mass Balance 20. ZALTOPROFEN a) Manufacturing Process Stage-1: Charge Methanol, 2-(2-(phenylthio)-5-propionylphenyl)acetic acid and Sulfuric acid. Heat reaction mixture for 65 oC for 5 hours. After completion distill out methanol cool reaction mixture and add toluene and water. Separate layers. Wash organic layer with Sodium Carbonate solution. Evaporate organic layer under vacuum. To the reaction mass charge Trimethylorthoformate, Zinc dust and heat at 50 oC.Charge bromine slowly. Upon completion cool the reaction mass and charge zinc dust. Heat reaction mass at 100 oC. Upon completion cool reaction mass and charge DM water and toluene. Separate layers. Wash organic layer with 20 % Sodium hydroxide solution. Acidify aqueous layer with dilute sulfuric acid. Cool reaction mixture to and filter slurry yield 5-(1-Carboxyethyl)-2- (phenylthio)phenylacetic acid. Stage-2: Polyphosphoric acid is charged in reactor, followed by 5-(1- Carboxyethyl)-2(phenylthio)phenylacetic acid. Charge Ethylene Dichloride and heat reaction mass to reflux at 83-85 oC for 30 minutes. Distill out Ethylene Dichloride. Reflux reaction mass for more 2 hours. After completion of reaction cool reaction mass to room temperature and quench the reaction mass in water. Heat reaction mass to 68-72 oC for 30 minutes. Separate layers and cool organic layer at 0-5 oC for 2 hours. Filter the product. Stage-3: Charge water and Ethanol in reactor and stir for 30 minutes. Charge Zaltoprofen crude at room temperature. Charge sodium carbonate solution slowly and stir for 1 hour. Neutralize reaction mass with Acetic acid. Filter the reaction mass and transfer filtrate to reactor. Charge more acetic acid and stir for 1 hour. Filter product and wash with DM water. Chemical Reaction: Mass Balance: Sr. Input No. Step-I 1 2-(2-(phenylthio)-5propionylphenyl)acetic acid 2 Methanol 3 Sulfuric Acid 4 Sodium Carbonate 5 Trimethyl Ortho Formate 6 Zinc Dust 7 Bromine 8 Sodium Hydroxide 9 Toluene 10 Water Total Step-II 11 Step-I 12 Polyphosphoric acid 13 EDC 14 Water 15 Total Step-III 16 Zaltoprofen Crude 17 Ethanol 18 Acetic Acid 19 Sodium Carbonate 20 Water 21 22 23 Total Quantity (Kg) Output Quantity (Kg) 1.414 Step-I 1.414 8.485 0.141 0.263 Methanol Rec Methanol Loss Toluene Rec. 7.828 0.657 3.939 1.232 Toluene Loss 0.303 0.061 0.919 0.778 3.242 11.101 28.636 Effluent Dist. Residue 14.162 0.333 Total 28.636 1.414 5.657 3.536 4.167 Step-II EDC Recover EDC Loss Effluent Dist. Residue Total 1.197 3.384 0.152 9.874 0.167 14.774 Zalttoprofen Ethanol Rec. Ethanol Loss Acetic Acid Rec. Acetic Acid Loss Effluent Dist. Residue CO2 Total 1.000 2.677 0.101 0.808 0.035 4.153 0.322 0.086 9.182 14.774 1.197 2.823 0.894 0.258 4.010 9.182 21. ONDANSENTRONE HYDROCHLORIDE Manufacturing Process: Stage 1: In a GLR, charge Iso Propyl Alcohol and Ondensetron Base. Heat up to 800C, add water 10% and Hydrochloric Acid 35%. Check clarity and check for pH 2, if Ok, filter the material through Sparkler Filter. Stage 2: In a GLR Collect filtrate and check its moisture and pH, if ok chill up to 50 C maintain for 5 hrs. Centrifuge the material. Unload and Dry Ondensentron Hydrochloride. Collect ML for recovery. Stage 3 (IPA Recovery): In a SSR, take ML of centrifuge and add caustic to obtain pH 9.0 and distilled out IPA completely. Charge water and cool to room temperature. Centrifuge the material and dry it. Recovered Ondansetron Base is used in Stage – I for next batch and ML is sent to ETP. Chemical Reaction Material Balance Sr. No. 1 2 3 4 Total Input Ondensetron Base IPA Water HCl Quantity (Kg) 90.91 354.54 136.36 21.45 603.26 Output Quantity (Kg) Ondensetron HCl Crop Base II Effluent 100.00 35.09 468.17 Total 603.26 22. Miconazole Nitrate and its intermediates: Manufacturing process and Chemical Reaction: Step-I 2,2’,4’ Trichloro acetophenone A charge 1,3-dichloro benzene100 Kg and chloroacetyl chloride 80 Kg and aluminum chloride 100Kg at A RT, Stir 30min. then stir 8 hour ,then cool to RT then dumping ice 400 kg ,centrifuge wash with 10 lit water , the wet cake:-170 Kg, Dry 65-700C Output dry :-140Kg O Cl Cl Cl + Cl O Cl AlCl 3 Cl Cl Step -II A charge Step -1 140 Kg and Add 180 kg of methyl alcohol and 25 liters of water at 20-250C. Added a solution of 10 Kg. of sodium borohydride in 20 kg water and 1kg sodium hydroxide to the above reaction mixture slowly at 20-250C in 5 hours. Allowed the reaction mixture temperature to 25-300C. Recovery of Methyl alcohol, Stirred the reaction mixture for 6 hours at 25-300C.add water 200kg, Filtered the precipitated solid and Centrifuge. Wet cake 160Kg, Output dry: - 140 Kg HO O Cl Cl Cl Cl NaBH Cl 4 Cl Step -III Step-2 140Kg was dissolved in toluene 360Kg. and Imidazole 43 Kg was added at 20-25° C. add caustic soda 25Kg , The temperature was raised to 50-55° C. and stirred for 3-5 hours, then cooled to 25-30° C. Reaction mass added into cold-water 200 lit. Reaction mixture was extracted and organic layer concentrated under reduced pressure to provide thick Filtered the precipitated solid and Centrifuge. Wet cake 160Kg, Output dry: - 150 Kg HO Cl H N Cl OH Cl + N N N Cl Cl Step -IV Step-3 150Kg was dissolved in toluene 450Kg..add caustic soda 25Kg , The temperature was raised to 50-55° C. and add slowly 2,4-Dichloro benzyl chloride 115 Kg was added 5-6 hrs and stirred for 3-5 hours, then cooled to 25-30° C. Reaction mass added into cold-water 200 lit. Reaction mixture was extracted and organic layer concentrated under reduced pressure to provide thick Filtered the precipitated solid and Centrifuge. Wet cake 250Kg, Output dry :- 225 Kg Cl Cl N N N Cl Cl Cl O + OH N Cl Cl Cl Cl Step -V A charge step-4 base 225 Kg and 390Kg Methyl alcohol at a RT , Then heat to clear solution temp 50-550C, then add activated charcoal 2kg stir 1 hour, filter then cool to RT, Then add Nitric acid 60 Kg heat to 550C, then cool to RT then child to 5-100C 1hour maintain. Then centrifuge wash to Methyl alcohol 10 lit, wet cake 275kg, Dry:- 250Kg Cl Cl N Cl N N O + Cl HNO3 . HNO3 Cl Cl ] N O Cl Cl MATERIAL BALANCE: Sr. Material Input No. Step-1 Qty (Kg) Material Output Qty (Kg) Drying Loss Effluent 2,2’,4’ Trichloro acetophenone 30 510 140 1 2 3 1,3-dichloro benzene Aluminum chloride Chloro Acetyl Chloride 100 100 80 4 Ice Water Total 400 680 Total 680 140 Effluent 213 NaOH MeOH Sodium Borohydrate Water Total 2 200 11 200 553 Resue Drying Loss Product 180 20 140 Total 553 Step-2 Imidazole Toluene Caustic Soda Water 140 43 360 25 200 Total 768 Effluent Drying Loss Re Use toluene Loss toluene Bottom Product Total 240 15 330 30 3 150 768 Step-3 2,4-DBC Toluene Caustic Soda Water 150 115 450 25 200 Total 940 Drying Loss Re Use toluene Loss toluene Bottom Effluent Product Total 25 400 50 10 230 225 940 Step-4 MeOH Activated Charcoal Nitric Acid 225 400 2 60 Total 687 Waste Charcoal Drying Loss Re Use MeOH Loss MeOH Bottom Product Total 4 25 360 40 8 250 687 Step-2 1 2,2’,4’ Trichloro acetophenone 2 3 4 5 Step-3 1 2 3 4 5 Step-4 Step-5 23. Ecanazole Nitrate Manufacturing Process: Miconazole base is synthesized from the reaction of 1-(2, 4-Dichloro phenyl)-2-(1HImidazol-1yl) Ethanol and 4-Chloro benzyl chloride in presence of sodium hydroxide and Tetrabutyl ammonium bromide as a catalyst and toluene as a solvent. The Miconazole Base treat with Nitric acid as in presence of Toluene give Nitrate salt of Miconazole Chemical Reaction N Cl N Cl N HO N Cl + NaOH + O Toluene,TBAB Cl Cl + Na Cl + H2O M.Wt.:58.44 MWt: 18.01 M.Wt: 40.00 Cl M.Wt.: 195.03 Cl Cl M.Wt.: 381.68 Toluene M.Wt.:257.11 N N HNO3 O Cl M.Wt.: 63.01 HNO3 Cl M.Wt.: 444.69 Mass Balance INPUTS for 100.0 Kgs RM 1-(2,4-Dichloro phenyl)2-(1H-Imidazol-1yl)Ethanol Toluene NaOH 4-Chloro benzyl Chloride TBAB Nitric acid Methanol D.M.water Activated Carbon Total Out Puts Product & By Product & waste QTY 80.0 Econazole Nitrate 100.0 300.0 35.0 50.0 2.0 20.0 30.0 200.0 1.0 718.0 Toluene Activated Carbon Residue Water 280.0 1.0 1.0 336.0. QTY (Kg) Total 718.0 24. ROSUVASTATIN CALCIUM Manufacturing Process: Step-I 4-Fluoro-Benzadehyde reacts with 4-Methyl-3-oxo-pentanoic acid ethyl ester in presence of Base to give Stage-1 as product. Step-II Sage-1 product reacts with S-Methyl iso thio urea and 2, 3Dichloro-5, 6-dicyano benzo quinone in presence of HMPA to give stage-2 as product. Step-III Stage-2 product reacts with meta-chloro peroxy benzoic acid to give Stage-4 as product and Meta chloro benzoic acid as by-product. Stage-4 Stage-3 product reacts with methyl amine in presence of Ethanol s solvent media to give Stage-4 as product. Stage-5 Stage-4 product reacts with Methane sulfonyl chloride in presence of Sodium hydride as catalyst to give Stage-5 as product. Stage-6 Stage-5 product undergoes reduction and oxidation in presence of Hydrogen gas to give Stage-6 as product. Stage-7 Stage-6 product reacts with methyl (3R)-3-(ert-butyldimethylsilyloxy)-5-oxo-6triphenylphosphoranylidene hexanoate. Stage-8 Stage-7 product reacts with Hydrogen fluoride in presence of Acetonitrile as solvent media to give Stage-8 as product. Stage-9 Stage-8 product reacts with Sodium Boro hydride undergoes hydrogenation to give Sage-9 as product. Stage-10 Stage-9 product reacts with Calcium chloride undergoes saponification to give Rosuvastatin Calcium as product. Chemical Reaction: Mass Balance 25. Desloratadine Manufacturing Process: Loratidine is refluxed with Methanol. The Material is then extracted in MIBK after Methanol removal. The product is then crystallized after distillation of MIBK to give Desloratidine. Chemical Reaction: Mass Balance: 26. LORATADINE AND ITS INTERMEDIATE Manufacturing Process: M-5 is reacted with Sulphuric acid and quenched to give M-6. M-6 is then chlorinated using Thionyl chloride and AlCl3 catalyst to give M-7. M-7 is then reacted with Grignard reagent and then acidified to give M-8. M-8 is then acidified and quenched to give Loratidine Crude. The crude is then purified first using Acetonitrile. The product is further purified using Ethyl acetate. Pure Loratidine is obtained by one more purification in Acetonitrile. Chemical Reaction: Mass Balance: Sr. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Particular M-5 Sulphuric Acid NaOH MDC Water SOCl2 DMF AlCl3 Hyflow Ethylene Dibromide THF Iodine HCl Chloroform Hexane Toluene NaHCO3 Acetonitrile Total Input Qty (kg) 5.8 1.8 6.5 161.04 25 6.63 0.27 1.45 1.26 0.47 36 0.01 3.1 62.3 4.5 58.72 3.36 7.88 386.09 Particular MDC Recovered MDC Loss THF Recovered THF Loss Chloroform Recovered Chloroform Loss Toluene Recovered Toluene Loss Acetonitrile Recovered Acetonitrile Loss Loratidine Effluent to ETP Solid to Incinerator Residue to Incinerator Spent Sulphuric Acid Total Output Qty (kg) 154.6 6.44 34.84 1.16 59.5 2.8 57.5 1.22 7.56 0.32 2.00 35.5 0.55 9 13.1 386.09 27. Gabapentine Manufacturing Process: Step-I 1,1-cyclodiacetic acid is condensed with urea in xylene. After completion, product is isolated by adjusting its pH with HCl to give stage-I. Stage 2: Stage-1 undergoes hoffman reduction with sodium hypochloride followed by cyclisation to give stage-II. Stage 3: Stage-II is converted into its hydrochloride salt with concentrate HCl. The product (Stage-III) is isolated by cooling the reaction mixture. Stage 4: Hydrochloride salt of stage-III is converted into gabapentin monohydrate by treatment with caustic solution. The product crystallises during caustic addition. Stage 5: Gabapentin monohydrate is dehydrated with methanol to get clear solution. It is treated with activated carbon and filtered. Gabapentin is isolated by cencentrating followed by cooling of reaction mixture. Product is filtered, washed and dried. Chemical Reaction: Mass Balance: 28. ALBENDAZOLE Manufacturing Process: 1. Charge Methanol, Ortho nitro aniline , Ammonium Thiocynate and cool to 0oC.Add Chlorine marinating temp between 0-5 oC ,then charge water and stirr for 1 hrs, centrifuge at R.T and wash with water to PH neutral. 2. Charge water , N-propanol ,charge STEP-1.Start addition of caustic lye slowly below 40 oC and heat to 50 oC . Maintain temp between 40-50 oC for 1/2 hrs and charge n- Propyl Bromide maintain the temperature at 50 oC . Maintain 4 Hrs at 62-65 oC .Distilled water Heat to 90 oC . Charge NACL while stirring. Settle & separate organic layer (TOP) 3. Charge STEP-2 with methanol stirring 15 minutes and heat to 50 oC . Start addition of NAHS slowly lot wise. Temp rises from 50 to 70 oC. Complete addition of NAHS from 60 -65 oC . Reflux 6-8 Hrs at 80-85 oC . 4. Start methanol recovery at temp 90 oC . Charge water and heat upto 85-90oC . Settle RM for 1 Hrs. Separate RM for 1 hrs , Separate Aqueous layer from bottom .Collect the top organic layer in Drums. Distilled out organic layer under vacuum I st cut removed upto temp 100 oC then distilled out product at temp upto 210 oC out product at temp upto 210 oC . 5. Charge water and cool to 8-10 oC . Charge Hydrogen Cynamide solution. Start simultaneous addition of MCF and Caustic lye slowly below 20 oC and PH should be 6-8 . Complete the addition below 20 oC. Stirring 1/2 Hrs. Check the absence of unreacted Hydrogen Cynamide. 6. Charge water , HCL , PART A, ,acetone and start addition of PART B. Heat to 65 o C . continue to reflux RM at 80-85 oC for 1HRs. Check PH of RM .It should be 4.00 to 6.0. Centrifuge Reaction mass at 80-85oC . Wash cake with Hot Water , Then wash with Methanol and again wash with Acetone to get the pure Albendazole. Chemical Reaction: Chemical reaction of ALBENDAZOLE STEP-1 NH4SCN Chlorine Gas NH4CL+H CL Methanol Ortho Nitro Aniline MOL WT :- 138.12 Ammonium Thiocynate MOL WT :: 76.122 5-THIOCYNO-2NITRO ANILINEMOL WT :-195.1985 NAOH CH3CH2CH2Br Methanol Step-2 INTERMIDIATE 5-THIOCYNO-2NITRO ANILINEMOL WT :- 195.1985 STEP -3 & 4 3,4 DIAMINOPROPYL THIO ANILINE (A) STEP-2 + NABR +NACN 2-NITRO 4 PROPYL THIO ANILINE NAHS MEOH Caustic Soda, Sodium Hydrosulphide, TOLUENE, Carbon, EDTA, SODIUM META BISULPHITE, Acetone METHANOL HCL 30% 1,2-DIAMINE5-PROPYL THIO BENZENE STEP -5 PART (B) (CYANAMIDE COMPLEX WITH CYANAMIDE SOLUTION) NAOH NC-NHCOOCH3 CAUSTIC SODA METHYL CYNO ESTER ( CYNO COMPOUND ) CH2N2 CYANAMIDESOLUTI ON (L-500) METHYL CHLORO FORMAT +HCL+ NAOH STEP-6 NC-NH NHCOOCH3 1,2-DIAMINE-5PROPYL THIO BENZENE CONDENSATION (A+B)=C METHYL CYNO ESTER (CYNO COMPOUND) METHANOL ACETONE ALBENDAZOLE Input (in Kgs) MATERIAL OUTPUT 1000 CRUDE 5-THIOCYNO-2NITRO ANILINE HCL NH4CL METHANOL ML TO ETP Total Output MATERIAL BALANCE Sr No. MATERIAL INPUT STEP-1 Ortho Nitro Aniline 1 2 4 5 6 1 2 3 4 5 6 7 1 2 3 4 5 6 Ammonium Thiocynate Methanol Chlorine Gas WATER Total Input 1168 5520 720 1000 9408 STEP 2 step-1 Caustic Soda N- Propanol N-Propyl Bromide 1400 860 3600 850 Toluene METHANOL 3600 3500 ML TO ETP NaBr STEP-2 OUTPUT RECOVERED METHANOL LOSS RECOVERED TOLUENE Sodium Hydrosulphide DILUTED TOTAL STEP -3 CYAANAMIDE SOLUTION (L-500) (L 4200 18010 LOSS TOLUENE TOTAL CAUSTIC SODA METHYL CHLORO FORMAT STEP 2 ACETONE WATER TOTAL 495 742 608 1400 2520 800 6565 Output (in Kgs) 1400 888 600 5520 1000 9408 8910 600 1400 3325 175 3420 180 18010 RECOVERD ACETONE LOSS ACETONE ML TO ETP RESIDUE OUTPUT QTY ABZ 2344 176 3000 105 940 TOTAL 6565 30. Cetrazine diHCl and its intermediates: Manufacturing Process and Chemical Reaction: Step-I P-chlorobenzophenone A charge chlorobenzene 100 Kg and Benzoile chloride 125 Kg and Aluminum chloride4 1kg at A RT, Then heat to 70-75 oC Stir 30min. Add Ice 120 kg then stir 1 hour , add slowly sodium hydroxide 35kg Stir 30min. , then centrifuge wet cake 175Kg. Dry Output 145. O STEP-1 Cl + O Cl + NaCl Cl Step-II 4-Chloro benzhydrol A charge p-chloro benzophenone 100 Kg and add methyl alcohol 135 Kg and sodium boro hydrate 7 Kg and caustic soda 1Kg at A RT, Stir 30min. Heat to reflux temp 600C ,Then add 100lit water cool to RT , wet cake 120 Kg, Dry 60-700C Out put dry :-100Kg STEP-2 OH O Cl Cl Step-III N- (4-chloro benzhydrol),N-(2-hydroxy ethyl) piperazine A charge 4-chloro benzhydrol 100 Kg and add toluen 235 Kg and thionyl chloride 85 Kg and scrubber caustic soda lye 200Kg and 100kg water at A RT, Stir 30min. Heat to reflux temp 600C ,Then add 80kg 2-hydroxy ethyl piperazine Stir 30min. Heat to reflux temp 600C ,then recovery of toluene, then add 100 lit Water then stir 1 hour , cool to RT ,centrifuge, the wet cake 120 Kg, Dry 60-700C Output dry :-100Kg STEP-3 OH N H N OH Cl N + N OH Cl Cl Cl Step-IV Cetrazine Base A charge N- (4-chloro benzhydrol),N-(2-hydroxy ethyl) piperazine100 Kg and add Sodium mono chloro acetic acid 38 Kgand Dimethyl formamide 185 Kg and Caustic potash 65 Kg at a RT, Stir 30min. Heat to temp 600C ,Then cool to 5 0C Stir 30min.add water 300kg ,centrifuge , the wet cake;-112 Kg, Dry 50-550C Output dry :-100Kg. STEP-4 OH OH O N N Cl N + O O N + NaCl Na Cl Cl Step-V Cetrazine Di HCl API A charge Cetrazine base 100 Kg and acetone 400kg at a RT , Then heat to clear solution temp 65-700C, then add activated charcoal 2kg stir 1 hour, filter and cool to RT, then child to 5100C 1hour maintain. Then start HCl gas 20kg pursing solid product isolated then check pH acidic , centrifuge, wet cake146 kg, Dry 110Kg STEP-5 OH O O O N OH N O N N + HCl . 2HCl Cl Cl MATERIAL BALANCE: Material Input Step-1 Chloro Benzene Benzoile Chloride Aluminium Chloride Sodium Hydroxide Ice Water Total Qty(Kg) 100 125 1 35 220 10 491 Material Output Qty(Kg) Effluent Drying Loss P-Chloro benzophenone 316 30 145 Total 491 Step-2 P-Chloro benzophenone Methyl Alcohol Sodium Borohydrate Sodium Hydroxide Water Total Step-3 100 135 7 1 100 343 Effluent Drying Loss 4-Chloro Benzhydrol 243 345 100 Total 343 4-Chloro Benzhydrol Toluene Thionyl Chloride Hydroxy Ethyl Piperazine Sodium Hydroxide Lye Water 100 235 85 80 200 200 230 315 20 215 20 100 Total Step-4 900 Effluent Scrubber waste water Drying Loss Reuse Toluene Loss Toluene N-(4-Chloro Benzhydrol),N-(2Hydroxy Ethyl)Piperazine Total N-(4-Chloro Benzhydrol),N-(2Hydroxy Ethyl)Piperazine Sodium Mono Chloro Acetate Dimethyl Formamide Potassium Hydroxide Water Total Step-5 100 Effluent 418 38 185 65 300 538 Cetrazine Base 120 Total 538 Acetone Activated carbon HCl gas Cetrazine Base 400 2 20 100 Total 522 Waste Carbon Reuse Acetone Loss Acetone Drying Loss Bottam Cetrazine Dihydrochloride Total 2 340 36 30 4 110 522 900 31. Lasamide Manufacturing Process: 2,4 Dichloro Benzoic acid is reacted with Chlorosulfonic acid(CSA) at elevated temperature. The product formed is isolated by quenching in ice water, the product is filtered and subjected to ammoniation to get Lasamide. Chemical Reaction: C7H4Cl2O2 + 2ClSO3H 2,4 Dichloro Benzoic acid CSA C7H3Cl3O4S + H2SO4 + HCl 2,4 Dichloro Benzoic acid Sulfonyl Chloride C7H3Cl3O4S + 3NH3 C7H8Cl2N2O4S + NH4Cl C7H8Cl2N2O4S + HCl C7H5Cl2NO4S + NH4Cl Mass Balance: Input 2,4 Dichloro Benzoic acid Chlorosulfonic acid Ammonia HCl Water Total Qty. (kg) 950 4720 720 1296 2320 10006 Output Product Effluent Dil. Sulphuric Acid Dil. HCl Ammonium Chloride Total Qty. (kg) 1000 1810 1316 4150 1730 10006 32. PIOGLITAZONE HYDROCHLORIDE Process Description 5-Ethyl-2-(2-(4- Nitro phenoxy)ethyl)pyridine (EPNB) is hydrogenated in presence of palladium catalyst to produce PGL-I, which is further diazotized using sodium nitrite solution in water to get diazotized PGL-I. It is further reacted with hydrogen bromide and methyl acrylate in presence of copper oxide (I) to get PGL-II. PGL-II is cyclized using thiourea and sodium acetate in methanol to give PGL-III (5-({4-[2-(5ethylpyridin-2-yl) ethoxy]benzyl}-2-imino-1,3-thiazolidin-4-one). PGL-III is reacted with hydrochloric acid in water to give PGL-IV ((5-({4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl}-1,3-thiazolidin-2,4-dione). PGL-IV is purified in DMF and water mixture to get PGL-V (pure Pioglitazone). PGL-V is isolated as a hydrochloride salt using concentrated Hydrochloride acid in ethanol water mixture as a solvent to get Pioglitazone hydrochloride. Chemical Equation Stage IA- Preparation of PGL-I NO 2 H3C + N 3 H2 O Hydrogen gas 5-ethyl-2-[2-(4-nitrophenoxy)ethyl]pyridine MW = 2.0 MW = 272.3 EPNB Palladium carbon NH2 H3C + 2 H2O O N 4-[2-(5-ethylpyridin-2-yl)ethoxy]aniline MW = 242.3 PGL-I MW = 18 Stage IB- Preparation of PGL-II NH2 H3C N O + O NaNO 4-[2-(5-ethylpyridin-2-yl)ethoxy]aniline + 2 Sodium nitrite MW= 242.3 PGL-I + 2 HBr H2C O Hydrobromic Acid MW= 69 CH3 Methyl acrylate MW= 81 MW= 86.08 Copper oxide(I) O H3C N + CH3 O B + NaBr + N2 2H 2 O r O m e th y l 2 - b ro m o - 3 - {4 - [2 (5 - e th y lp y rid in - 2 - y l)e th o x y ]p h e n y l}p ro p a n o a te Sodium bromide MW = 392.28 Nitrogen gas MW = 103 Water MW = 28 MW = 18 P G L - II Stage IC- Preparation of PGL-III O H3C CH3 O Br S + + H2N N O methyl2-bromo-3-{4-[2- H3C ONa O NH2 (5-ethyl pyri di n-2-yl)ethoxy]phenyl}propanoate Thiourea MW= 392.28 Sodium Acetate MW= 76.1 MW= 82.03 PGL-II H3C N O O 5 - { 4 - [ 2 - ( 5 - e t h y l p y r i d i n - 2 - y l) e t h o x y ] benzyl}-2-imino-1,3-thiazolidin-4-o ne MW= 355.4 PGL-III Stage II- Preparation of PGL-IV S NH H3C + N H + 2 HCl O 2 + KHCO 3 N H O O 5-{4-[2-(5-ethylpyridin-2-yl) ethoxy]benzyl} 2-im ino- 1,3-thiazolidin- 4-one MW= 355.4 Potassium Bicarbonate MW= 36.46 MW = 18 MW= 100.11 PGL-III S NH + N + NaBr H Sodium Bromide O N O O N H MW= 103 + Acetic Acid CH 3 OH NH 4 Cl + CO 2 MW= 32.0 KCl Potassiumchloride MW= 53.5 + Methanol MW= 60.0 AmmoniumChloride 5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1, 3-thiazolidine-2,4-dione MW= 356.43 + OH O S H3C H3C MW= 74.5 + H2O PGL-IV Carbondioxide MW= 44 MW= 18 Stage III- Preparation of PGL-V S S O H3C N O O O H3C DMF N H N O O 5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1, 3-thiazolidine-2,4-dione 5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1, 3-thiazolidine-2,4-dione MW= 356.43 MW= 356.43 PGL-IV PGL-V Stage IV- Preparation of Pioglitazone Hydrochloride S O H3C N N O O HCl + H Hydrochloride 5-{4-[2-(5-ethylpyridin-2-yl)ethoxy]benzyl}-1, 3-thiazolidine-2,4-dione MW= 356.43 PGL-V MW=36.5 S O H3C N O HCl O MW= 392.89 Pioglitazone Hydrochloride N H N H Mass Balance: S tep-1 - PZ1 PR EPARA TION I NP UT : Raw Material ME P Met hanol PFA Fo rmi c Charc oal Total I NP UT : Raw Material Mas s In put , Kg s 4.86 1.35 1.8 4 0.2 5 0.0 1 8.31 OUTP UT : Prod uct Mas s Total In put , Kg s 8.31 Distillation Total Output, Kgs 8.31 Reaction ( 8 days) 8.31 8.31 OUTP UT : Prod uct P2 1 MEP Methanol Loss Met hanol Residue to I nc. * Total Output, Kgs 1.08 3.45 0.56 0.79 2.43 8.31 OUTP UT : Prod uct Mas s Output, Kgs 6.54 S tep2 - PZ 2 PR EPA RATION I NP UT : Raw Material P2 1 In put , Kg s 1.08 Toluene TE A MSC Total I NP UT : Raw Material Water Mas s Total 3.71 0.84 0.91 6.54 In put , Kg s 10. 80 6.54 17.340 Reaction Total Water Washing 6.54 OUTP UT : Prod uct Ma ss Aqueons Layer t o ETP * Total Output, Kgs 6.3 3 11.01 17.340 OUTP UT : Prod uct Mas s Output, Kgs 12.45 S tep 3 - PZ3 PR EPARA TI ON I NP UT : Raw Material PZ 2 I PA H2O In put , Kg s 6.33 3.41 0.29 4OH benzal dehyde K 2 CO 3 Total I NP UT : Raw Material Mas s Water Toluene Total I NP UT : Raw Material Mas s NaOH H2O Total Reaction 1.00 1.42 12. 45 In put , Kg s 12. 45 10. 80 2.06 25. 31 In put , Kg s 8.710 0.36 8.39 17. 46 Total Water Washing OUTP UT : Prod uct Aqueous t o ETP * Mas s 12.45 Output, Kgs 16.60 8.71 Total Cau stic Wash in g OUTP UT : Prod uct Aqueous t o ETP * Mas s Total 25.31 Output, Kgs 8.75 8.71 17.46 S tep 4 - PZ 4 PR EPARA TI ON I NP UT : Raw Material H2O Acet ic Aci d Thio Urea Total 1.25 0.96 7.02 I NP UT : Raw Material Mas s Water Total In put , Kg s 6.780 0.960 7.740 I NP UT : Raw Material Wet Cake In put , Kg s 1.47 Total OUTP UT : Prod uct Ev aporation Los s In put , Kg s 4.81 1.47 Reaction Filtration D rying Output, Kgs 0.24 Mas s 6.78 Total 7.02 OUTP UT : Prod uct ML t o E TP * Wet Cake Total Output, Kgs 6.27 1.47 7.740 OUTP UT : Prod uct Vapours Dry Cake Total Output, Kgs 0.22 1.25 1.47 S tep 5- PZ 5 PREPARATI ON I NP UT : Raw Material Mas s Met hanol In put , Kg s 8.71 18. 73 Total I NP UT : Raw Material Mas s P Z4 P iperidue Total D is tillation 27. 44 In put , Kg s 21. 67 1.25 0.28 23. 20 OUTP UT : Prod uct Mas s Output, Kgs 23.20 Total 23.20 OUTP UT : In put , Kg s 23 .2 0 2.39 0.57 Total I NP UT : Raw Material Wet Cake Output, Kgs 4.44 1.33 21.67 27.44 Reaction I NP UT : Raw Material Ma ss Water Met hanol OUTP UT : Prod uct Toluene R ec. D ist illation Loss Mas s Total Filtration & Solv en t Recov ery 26. 16 In put , Kg s 1.44 Total Prod uct Loss MeOH Rec . Wet Cake R eidue t o I nc * Total Drying 1.44 Output, Kgs 9.86 13.51 1.44 1.35 26.16 OUTP UT : Prod uct Vapours Loss D ry Cak e Total Output, Kgs 0.21 1.23 1.44 OUTP UT : Prod uct Mas s Output, Kgs 27.97 S tep 6- PZ6 PR EPA RATI ON I NP UT : Raw Material PZ5 THF DMG Cobalt ous Ch. NaOH Na BH4 DMF Water Total In put , Kg s 1 .23 3.73 0.16 0.01 0.10 0.26 3.28 19. 20 27. 97 I NP UT : Raw Material Ma ss E thyl Acet ate In put , Kg s 27 .9 7 16. 60 Total Reaction Total Extraction & S olv en t recovery 44. 57 I NP UT : Raw Material Mas s Ac etic Acid Total In put , Kg s 36. 27 2.58 38. 85 I NP UT : Raw Material Mas s I PA Total In put , Kg s 38 .8 5 0.98 39. 83 I NP UT : Raw Material Wet Cake In put , Kg s 1.38 Total Precip itation OUTP UT : Prod uct EA Rec . Mas s Loss R esidue to I nc * Total Output, Kgs 8.30 36.27 0.88 0.88 44.57 OUTP UT : Prod uct Mas s Output, Kgs 38.85 Total Fitration Drying 1.38 27.97 38.85 OUTP UT : Prod uct ML t o E TP * Wet Cake Total Output, Kgs 38.45 1.38 39.83 OUTP UT : Prod uct D ry Cak e Vapour Total Output, Kgs 1.1 1 0.27 1.38 OUTP UT : Prod uct Mas s Output, Kgs 8.06 S tep 7- PZ HCl PR EPARA TI ON I NP UT : Raw Material P Z6 Met hanol HCL Carbon Total I NP UT : Raw Material Ma ss Hyf low Total In put , Kg s 1.11 6.07 0.85 0.03 8.06 In put , Kg s 8 .06 0.01 8.07 Reaction Total OUTP UT : Prod uct S park ler Filtration C ake t o I nc in. * Filt erate Total 8.06 Output, Kgs 0.05 8.02 8.07 Sparkler Filtration INPUT : Raw Material Filterate Total INPUT : Raw Material Mass MeOH Wash Total INPUT : Raw Material Wet Cake Input , Kgs 8.02 Total Output, Kgs 3.30 0.33 4.39 8.02 Centrifuge & Solvent Recovery OUTPUT : Product MeOH Rec. . Loss Residue t o I nc. * Wet Cake Total Output, Kgs 1.71 1.87 0.43 1.20 5.21 Drying OUTPUT : Product Vapour Dry Cake Total Output, Kgs 0.18 1.02 1.20 Sifte r & Mic ronisation OUTPUT : Product Loss PZ Pure Total Output, Kgs 0.02 1.00 1.02 8.02 Input , Kgs 4.39 0.82 5.21 Input , Kgs 1.20 Total INPUT : Raw Material Dry Cake Crystallisation OUTPUT : Product Dis tillat ion Dis tillat ion Los s Mass Total 1.20 Input , Kgs 1.02 1.02 33. MESALMINE Brief Manufacturing Process: STEP 1 Preparation of 2-Hydroxy-5-Nitro Benzoic Acid With Nitration of Ortho Chloro Toluene receive the Ortho Chloro Benzoic Acid again the nitration of the Ortho Chloro Benzoic Acid we will receive the 2-chloro-5- nitro benzoic acid. To a stirred solution of potassium hydroxide (70 kg, 1250 mol) and water (250 l) was added 2chloro-5- nitro benzoic acid (50 kg ,248 mol) over a period of 20 minutes between 25 to 30 0C in an autoclave. The reaction mixture was heated to 125-130oC , stirred At the same temperature for 5 hours under 2.5 kg /cm2. The reaction mass was cooled to 25 oC and acidify to PH 1.0-2.0 using hydrochloric acid (85 L) , stirred for 1 hour. The precipitated solid was filtered and washed with water (150 L) , and the cake slurried in water (300 L) at 30 Oc for 1 hour, filtered, washed with water ( 150 L) and dried at 65 oC for 10 hours to afford product 43.5 kg yield :- 43.5 kg (96 % ) purity :- 99.87 % 1H NMR ( 400 MHZ, DMSO): DELTA 11.2 (s,1H), 8.5 (m,2H), 7.3 ( s ,1H),5.2 (s,1H).MS m/z 183; Anal Calcd.for C7H5NO5 STEP 2 Preparation of 5-amino-2-hydroxy benzoic acid 2-Hydroxy-5-Nitro Benzoic Acid (40 kg,218 mol) was added slowly to a stirred mixture of water (320 L ) and sodium carbonate (16.3 kg, 153 mol) . stirred for 30 minutes and the mass ph maintained between 8.0 and 9.5 . 10 % Raney Nickel (8 L) along with water (80 L) was added to the above solution. The resultant mixture( 130 L) was added to the mass at 25oC , Stirred for 30 minutes . The catalyst was filtered through celite , and washed with water (80L) . the solution was acidified to Ph 2.5-3.0 with hydrochloric acid (33L) and stirred for 1 hour. The obtained compound was filtered , washed with water (40 L ). To the solution of wet cake and water (560 l ) and hydrochloric acid (41 L) . active charcoal (2.8 kg) was added, and the contents were heated to 70 o C , maintained at the same temperature for 2 hours. Filtered the total solution through celite, washed with water (28 L) . Active charcoal (2.8 kg) was added to the filtrate, stirred at a temperature of 70 oC for 2 hours, filtered through celite and washed with water (28L) . to the obtained filtrate, Ph was adjusted to 3.0-3.5 with aq.sodium bicarbonate solution (15 L ) , stirred for 1 hour, filtered the solid and washed with water (42 L), dried the solid at 80 OC for 9 hours to give the product as off white colored p powder. Yield :- 27.5 kg (82 % ) Purity : -(99.9%) (99.9%) CHEMICAL REACTION 2-chloro-5- nitro benzoic acid 2-Hydroxy-5-Nitro Nitro Benzoic Acid KOH + → + HYDROCHLORIC ACID 2-Hydroxy-5-Nitro Benzoic Acid Sodium carbonate+ MESALAMINE CAS number :- 89-57-6 Formula :- C7H7NO3 Raney nickel + → Sodium hydroxide + (5-amino-2-hydroxy hydroxy benzoic acid) + Hydrochloric acid + Charcoal + sodium bicarbonate MATERIAL BALANCE Sr. MATERIAL INPUT No. STEP 1 1 2 3 4 POTASSIUM HYDROXIDE 2-chloro-5- nitro benzoic acid HYDROCHLORIC ACID WATER TOTAL STEP 2 1 step 1 crude INPUT IN KG KG 70.00 MATERIAL OUTPUT OUTPUT IN KG crude 43.5 50.00 WATER 150 85.00 HCL 74 150.00 SOLID WASTE 87 355.00 43.50 354.5 2 3 4 5 6 7 SODIUM CARBONATE RANEY NICKEL SODIUM HYDROXIDE HYDROCHLORIC ACID CHARCOAL SODIUM BICARBONATE TOTAL 16.30 16.9 130.00 SODIUM CARBONATE RANEY NICKEL SODIUM HYDROXIDE 74.00 WATER 110 5.60 mesalamine crude 27.5 TOTAL 292.4 8.00 8 130 15.00 292.4 33. RABEPRAZOLE SODIUM Manufacturing Process: Stage-1 2, 3-Lutidine is reacted with Hydrogen Peroxide in presence of Acetic Acid to give N-Oxide it further reacts with Nitration mixture (Nitric Acid + Sulfuric Acid) to give Stage-1 Stage-2 Stage-1 is reacted with 3-Methoxy-1-Propanol and Sodium Hydroxide to get Stage-2 Compound Stage-3 Stage-2 Compound is reacted with Acetic Anhydride, Sodium Hydroxide and Hydrochloric Acid to get Stage-3 Compound Stage-4 Stage-3 Compound is reacted with Thionyl Chloride, 2Mercapto benzimidazole and sodium hydroxide in the presence of MDC as a solvent media to give tage-4 as product. Stage-5 Stage-4 Compound is reacted with Sodium Hypochlorite to get Rabeprazole Base Stage-6 Stage-5 reacts with Sodium hydroxide to get Rabeprazole Sodium Chemical Reaction: Mass Balance: 34. FEBUXOSTAT Process Description: Ethyl-2-(3-cyano-4-isobutoxyphenyl)-4-methyl-5-thiazolecarboxylate (NV07-3) is hydrolyzed with sodium hydroxide solution in isopropyl alcohol to furnish the product. The pH is adjusted with hydrochloric acid and solid is separated by filtration as Febuxostat crude. Febuxostat (crude) is dissolved in acetone and charcoalized. After filtration, acetone is distilled out and solid is filtered to give Febuxostat. Chemical Equation Mass Balance: Sr. No. 1 2 3 4 5 6 7 8 Particular Ethyl-2-(3-cyano-4isobutoxyphenyl)-4-methyl-5thiazolecarboxylate Methanol Toluene Caustic soda flakes HCl Water Total Input Qty (kg) 1.250 12.50 7.50 0.125 0.250 5.000 26.625 Particular Product Methanol Recover Methanol Loss Toluene Recover Toluene Loss Effluent Dist. Residue Loss Total Output Qty (kg) 1 12.00 0.50 7.25 0.25 4.375 0.750 0.500 26.625 35. ITOPRIDE HYDROCHLORIDE Process Description Verateric acid and Thionyl Chloride is reacted in toluene medium. At the end of the reaction any excess of thionyl chloride is removed by purging nitrogen in the solution. The crude VC (Vertroyl Chloride) obtained is used as such in the next step. ITO ((2-[4 - aminomethyl) phenoxy] N,N-dimethyl ethanamine) is reacted with VC solution. The crude product is isolated by removal of the solvent. Crude product (Itopride Base) is treated with carbon in hot acetone. After removal of carbon, addition of acetone HCl leads to formation of the Itopride HCl. Chemical Equation Mass Balance: Sr. No. 1 2 3 4 5 6 7 8 9 10 Particular Veratric acid Thionyl chloride Toluene 4-[2-(Dimethylamino) ethoxy]Benzyl amine Caustic soda flakes IPA IPA HCl Methanol Acetone Water Total Input Qty (kg) 0.667 0.667 3.270 0.667 0.095 2.857 0.317 0.159 0.635 8.095 17.429 Particular Product Toluene Recover Toluene Loss IPA Recover Output Qty (kg) 1 3.111 0.159 2.794 IPA Loss Dist. Residue Effluent HCl Gas SO2 Gas 0.063 0.467 9.445 0.147 0.234 Total 17.42 36. Celecoxib Manufacturing Process: • Charged water in Reactor at RT. Charged 4 SPH and Dione Deri in Reactor. The reaction mixture was heated and stirred well. Cool the RM and Filter the Product. • Charged Toluene and wet cake in above reactor again. Heat the RM and stir well for several time. The organic layer were washed with water add Activated carbon at stirred under heating. • Filter the RM with Sparkler. The filtrate was cooled. The separated solid was filtered and dried Chemical Reaction: Mass Balance: Sr. Input No. 1 4 SPH 2 Dione Deri 3 Toluene 4 Carbon 5 Water 6 Total Quantity (Kg) Output Quantity (Kg) 0.70 0.65 2.80 0.01 1.60 Final Product Toluene (Recd) Distillation + Drying Loss Residue Carbon Waste Effluent 1.00 2.65 0.19 0.03 0.02 1.88 5.77 Total 5.77 37. CLOPIDOGREL BISULPHATE Manufacturing Process: STAGE 1: • Starting materials amino(2-chlorophenyl)acetic acid ,methanol, Sulfuric acid are added into the reaction vessel and agitated until reaction is completed. • Methanol is recovered from the reaction mass by distillation and some of the same is lost as vapor during the operation. • Water and Dichloro methane are added into the reaction mass and adjust PH to neutral with liquor ammonia. • Two layers namely MDC layer and aqueous layer are obtained. • Aqueous layer is sent to ETP. • MDC (Dichloro methane) layer is then distilled to recover MDC wherein vapor loss occurs during the operation. • Stage 1 product is further isolated by continuing distillation. STAGE 2: • Starting materials thiophene-2-ethanol, toluene, p – toluene sulphonyl chloride, water, sodium hydroxide solution are added into the reaction vessel and stirred until reaction is completed. • Two layers toluene layer and aqueous layer are obtained. Aqueous layer is further sent to ETP. • Toluene layer is then distilled to recover toluene wherein vapor loss occurs during the operation. • Stage 2 product is further isolated by continuing distillation. STAGE 3: • Starting materials Stage 1 product, stage 2 product, acetonitrile, dipotassium phosphate are added into the reactor and stirred until the reaction is completed. • Acetonitrile is recovered from the reaction mass by distillation and some of the same is lost as vapor during the operation. • Ethyl acetate is added into to the reaction mass and agitated to clear solution. • Further water is added to obtain layer separation. • Two layes namely ethyl acetate layer and water layer are obtained. And water layer is sent to ETP. • Further conc. Hydrochloric acid is added to the ethyl acetate layer for precipitation and then filtered through centrifugal filter. • The wet cake so obtained is dried to obtain final product. • Filtrate is then distilled to obtain ethyl acetate and remaining effluent is sent to ETP. STAGE 4: • Starting materials couple ester, water, paraformaldehyde is charged into the reaction vessel and is agitated. • Further dichloro methane and water are added to the reaction mass and then adjust PH acidic with liquor ammonia. • Namely MDC layer and water layer are obtained. • Water layer is sent to the ETP. • MDC layer is then distilled to recover MDC. Wherein vapor loss occurs during the operation. • Stage 1 product is further isolated by continuing distillation. STAGE 5: • Starting raw materials stage 4 product, acetone, Tartaric Acid are charged into the reaction vessel and are stirred for longer time. • Entire mass is then filtered by centrifugal filter and wet cake so obtained is dried to obtain dry cake.. • The filtrate is sent for solvent recovery. • Water and dichloro methane are charged into the reaction vessel & then dry cake obtained is charged. • Further PH is adjust to alkaline by sodium carbonate solution to obtain layer separation. • Namely MDC layer & water layer are obtained. • Water layer is sent to ETP.MDC layer is then distilled to recover MDC wherein vapor loss occurs during the operation. • Stage 2 products are further isolated by continuing distillation. STAGE 6[Final]: • Stage 2 product, acetone, activated carbon are charged into the reaction vessel and entire mass of the reaction vessel is filtered through the neutch filter. • Further con. Sulfuric acid is added slowly to the reaction mass for crystallization. • It is further filter through centrifugal filter. • The wet cake so obtained is dried to obtain final product. • The filtrate is used in next batch for obtaining second crop. • The dried product is finally packed. CHEMICAL REACTION: STAGE 1: O OH O Cl O Cl CH3 Methanol/H2SO4 NH2 NH2 amino(2-chlorophenyl)acetic acid methyl amino(2-chlorophenyl)acetate STAGE 2: CH3 S Thiophene-2-Ethanol OH + O S Cl O para toluene sulphonyl chloride O H3C S O O S Chloro phenyl glycine methyl ester tartarate salt STAGE 3: O O Cl O CH3 H3C S + NH2 O O S 2-(2-thienyl)ethyl 4-methylbenzenesulphonate methyl amino(2-chlorophenyl)acetate Ethyl acetate/HCL Cl O NH O .HCL H3C S methyl (2R)-(2-chlorophenyl){[2-(2-thienyl)ehtyl]amino}acetate hydrochloride STAGE -4 : Cl Cl O P-Formaldehyde O N NH O O H3C H3C S S methyl (2-chlorophenyl)(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate stage 3 STAGE – 5 : Cl O Cl Tartaric Acid O N N O H3C S Stage 4 STAGE – 6: Material Balance: O S H3C methyl (2R)-(2-chlorophenyl)(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)ethanoate Qty (in kg) Sr. No. 1.25 1 Recovered Methanol 3.75 3.95 0.7 5.30 4.98 0.62 16.80 2 3 4 5 6 Loss Methanol Recovered MDC Loss MDC ML to ETP Stage 1 Output TOTAL 0.20 4.48 0.5 6.87 1.00 16.80 STAGE 2 Thiophene-2-Ethanol p-toluene sulphonyl chloride Toluene Water Sodium hydroxide 0.5 1.05 3.12 4.5 1.25 1 2 3 4 5 Recovered Toluene Loss Toluene ML to ETP Stage 2 Output Residue 2.93 0.16 6.30 1.00 0.03 TOTAL 10.42 TOTAL 10.42 STAGE 3 Stage 1 Stage 2 Acetonitrile Dipotassium phosphate Ethyl acetate water HCL TOTAL 1.25 1.00 6.30 0.87 5.60 2.00 0.85 17.87 1 2 3 4 5 6 7 Recovered Acetonitrile Loss Acetonitrile Recovered Ethyl acetate Loss Ethyl acetate ML to ETP Residue Stage 3 Output TOTAL 5.98 0.32 5.26 0.28 4.97 0.06 1.00 17.87 STAGE 4 Stage 3 Water P-Formaldehyde MDC Liq. Ammonia 1.50 12.00 0.53 11.9 0.60 1 2 3 4 Recovered MDC Loss MDC ML to ETP Stage 4 product 10.71 1.19 13.53 1.10 Sr. Material Input No. STAGE 1 1 amino(2-chlorophenyl)acetic acid 2 methanol 3 Potassium salt 4 Water 5 MDC 6 Liq. ammonia TOTAL 1 2 3 4 5 1 2 3 4 5 6 7 1 2 3 4 5 Material Output Qty (in kg) 1 2 3 4 5 6 1 2 3 4 TOTAL STAGE 5 Stage 4 Acetone Tartaric acid Water MDC Sodium carbonate TOTAL 26.53 1.10 11.00 0.82 2.70 6.65 0.70 22.97 STAGE 6 Stage 5 Acetone Activated carbon Sulfuric acid 1.00 4.74 0.15 0.31 TOTAL 6.20 TOTAL 26.53 1 2 3 4 5 6 Recovered Acetone Loss Acetone Recovered MDC Loss MDC ML to ETP Stage 5 Output TOTAL 9.90 1.10 5.98 0.67 4.32 1.00 22.97 1 2 3 4 Recovered Acetone Loss Acetone Spent carbon Stage 6 Output 4.50 0.24 0.46 1.00 TOTAL 6.20 38. AMRODAFINIL Manufacturing Process The manufacturing process for the above mentioned products involves chemical synthesis utilizing mainly organic chemicals as raw materials in batch process. These batch processes are used to produce active pharma ingredients with unique physical and pharmacological properties. Typically, a series of chemical reactions are performed in multi-purpose reactors and the products are isolated by extraction, crystallization and filtration. The finished products are usually dried, and milled. Chemical Reaction: Mass Balance: 39. QUETIAPINE FUMARATE: Manufacturing Process: Quetiapine stage-1 & 2 2-Amino dimethyl sulfide reacts with phenylchloro formate to give carbamate product which cyclize in the presence of phosphoric acid to give quetiapine stage 1 & 2. Quetiapine stage-F Quetiapinefumarate stage – 2 reacts with N,N-Dimethyl aniline in presence of phosphorous oxychloride will further reacts with 1-hydroxy ethoxy ethyl piperazine using triethanolamine as catalyst in toluene as media. Finally product will be isolated by distillation of toluene and addition of Methanol and fumaric acid solution to form Quetiapine fumarate. CHEMICAL REACTION: O NH2 Cl Phenyl chloroformate Molecular Formula:C7H5ClO2 Formula Weight:156.57 2-(phenylsulfanyl)aniline Molecular Formula = C12H11NS Formula Weight = 201.29 H N O + S O S Quetiapine stage-1 & 2 Molecular Formula = C13H9NOS Formula Weight = 227.28166 OH + + Phenol Molecular Formula:C6H6O Formula Weight:94.11 HCl Hydrochloric acid Molecular Formula:HCl Formula Weight:36.5 MASS BALANCE: Input 2- Amino diphenyle sulfide Sodium Hydroxide flakes Process water Toluene Phenyl chloroformate Hydrochloric acid Polyphospheric acid Acetone Total Ton 1.11 0.32 7.80 6.67 1.27 0.66 8.89 3.48 30.19 Output Air Waste Aqueous waste Toluene Recovery Toluene Loss Acetone Recovery Acetone Loss distillation residue Product Total Ton 0.06 19.99 6.33 0.33 3.33 0.14 0.33 1.00 30.19 MASS BALANCE : Input Dibenzo [b,f] [1,4] Thiazepin -11(1 OH)- ONE N,N- Dimethyl ANILINE Phosphorous oxychloride Hydrochloric acid Sodium Sulphate Process water Toluene Triethanolamine Hydroxy ethoxyrthyl piparazine Sodium bicarbonate 1 N HCl Hyflosupercel Methanol Fumaric acid Total Ton 0.6 0.4 0.3 0.5 0.1 6.5 5.2 0.4 0.4 0.1 0.1 0.0 7.7 0.2 22.6 Output Air Waste Aqueous waste Toluene Recovery Toluene Loss Methanol Recovery Methanol Loss distillation residue Spent hyflow Product Ton 0.03 8.42 4.90 0.26 7.43 0.31 0.19 0.03 1.00 Total 22.6 40. ATORVASTATIN Manufacturing Process: Stage: 1 Preparation of (5R)-1,1-Dimethylethyl 6-Cyano-5hydroxy 3-oxo-hexanoate (ATVS1) (R)4Cyano-3-hydroxy butyric acid, ethyl ester is reacted with tert butyl acetate in the presence of LDA at low temp to get ATVS1. Stage: 2 Preparation of [R-(R*, R*)]-1, 1-Dimethylethyl 6-Cyano-3, 5-dihydroxy hexonate (ATVS2), ATVS1 is reacted with Sodium Borohydride in THF and MeOH in the presence of Diethyl Methoxy Borane. After completion of reaction, reaction mass is quenched with acetic acid. After work up affords ATVS2. Stage: 3 Preparation of (4R-Cis)-1, 1-Dimethylethyl 6-Cyanomethyl-2, 2-dimethyl-1, 3-dioxane4-acetate (ATVS3), ATVS2 is reacted with Acetone in presence of Methane Sulphonic Acid using 2,2- Di Methoxy propane. And then it is neutralized with 5% NaHCO3 solution then extracted with Ethyl Acetate. After distillation of Ethyl Acetate MeOH & Water to get ATVS3. Stage: 4 Preparation of (4R-Cis)-1,1-Dimethylethyl 6-(2-amino ethyl)-2,2-dimethyl-1, 3dioxane-4-acetate (ATVS4), ATVS3 is reduced with Methanolic Ammonia in presence of Raney Nickel and Hydrogen gas, then catalyst is filtered off and the filtrate is concentrated to give oily mass ATVS4. Stage: 5 Preparation of [R-(R*, R*)]-2(4-Fluorophenyl)-β, 8-dioxane-5-(1-methylethyl)-3phenyl-4-[(phenyl amino)Carbonyl]-1H-Pyrrol-1tert –butyl heptanoic ester (ATV8), ATVS4 is condensed with (+) 4-fluoro-α-2-methyl-1-oxopropyl]χ-oxo-N-β- Diphenyl-benzene butane amide in presence of Pivalic acid using Toluene, Heptane and THF at. After completion of reaction work up is done with 0.1N NaOH & 0.1N HCl. Organic layer is evaporated which is crystallized in IPA and Water to get ATV8. Stage: 6 Preparation of Atorvastatin Calcium Acidic and basic hydrolysis of ATV8 with HCl and NaOH gives sodium salt of Atorvastatin, which is treated with Aqs Calcium Acetate to give Atorvastatin Calcium in Aqs Methanol. CHEMICAL REACTION MATERIAL BALANCE Sr. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Particular Ethyl-4-Cyano-3-hydroxy butanaote THF Diisopropyl amine N-Butyl Lithium Tert-Butyl acetate HCl Ethyl Acetate NaCl Methanol DEMB (50 % Soln) Sodium Borohydride Acetic Acid Dimethoxy Propane Methane Sulphonic Acid Sodium Bicarbonate n-Hexane DM Water 18 19 20 21 22 Raney Nickel Pivalic Acid Toluene Activated Carbon Methyl Tert Butyl Total Input Qty (kg) 1.00 17.567 1.22 13.60 1.68 0.76 31.57 1.20 25.243 0.70 0.44 0.98 1.81 0.03 2.00 5.20 22.38 Sr. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 1.00 0.240 9.379 0.100 7.410 18 19 145.496 Particular Output Qty (kg) Product 1.85 THF Recovered 17.04 THF Loss 0.527 N-Butyl Lithium Recovery 12.92 N-Butyl Lithium Loss 0.68 H2 gas 0.09 Spent Catalyst 1.5 Spent Carbon 0.05 Ethyl Acetate Recovered 30.94 Ethyl Acetate Loss 0.63 Methanol Recovered 24.61 Methanol Loss 0.63 n-Hexane Recovered 5.12 n-Hexane Loss 0.08 Toluene Recovered 9.19 Toluene Loss 0.189 Methyl Tert Butyl 7.04 Recovered Methyl Tert Butyl Loss 0.37 Effluent 32.04 Total 145.496 41. ARIPIPERAZOLE: Manufacturing Process: Stage-1 7-HDQ react with 1-bromo-4-chlorobutane to form 7-(4-chlorobutoxy)-3,4-dihydroquinoline-2one. Stage-2 Stage-1 react with DCCPP hydrochloride in presence of TEA and TBAB to form Aripiperazole crude. Stage-Final Aripiperazole crude purify by usingAcetonitrile and isobutanol to form pure Aripiperazole. CHEMICAL REACTION: Cl Na + O N H OH Cl OH O N H O Br Molecular Formula: C9H11NO2 Formula Weight: 165.18914 Molecular Formula: C4H8BrCl Formula Weight: 171.46332 Molecular Formula: C13H18ClNO2 Formula Weight: O Cl Cl O N H O H N O Cl + 255.74052 TEA N N H N HCl N Molecular Formula: C13H18ClNO2 Molecular Formula: C10H13Cl3N2 Formula Weight: Formula Weight: 255.74052 Cl 267.58262 Cl Molecular Formula: C23H29Cl2N3O2 O O H N Formula Weight: 450.40126 H N O O N Purification N N N Cl Cl Cl Molecular Formula: C23H29Cl2N3O2 Molecular Formula: C23H29Cl2N3O2 Cl Molecular Formula: C23H29Cl2N3O2 Formula Weight: 450.40126 MASS BALANCE: Input 7- Hydroxy -3,4- dihydroQuinoline 1- Bromo -4- Chloro Butane Ton 0.74 4.44 Sodium Hydroxide 0.24 n- Propanol Cyclohexane Process water Triethylamine DCPP HCl Methanol 3.70 1.48 9.26 0.59 0.59 0.37 Total 21.43 Output Air Waste Aqueous waste 1- Bromo -4- Chloro Butane Recovery 1- Bromo -4- Chloro Butane Loss n-Propanol Recovery n-Propanol Loss Cyclohexane Recovery Cyclohexane Loss Methanol Recovery Methanol Loss distillation residue Product Total Ton 0.06 10.22 4.22 0.22 3.56 0.15 1.44 0.04 0.36 0.01 0.15 1.00 21.43 42. AMLODIPINE BESYLATE Manufacturing Process: STAGE 1 • Charge Methanol, Phthaloyl Amlodipine and Mono Methyl amine in Reactor. Heat the reaction mass under stirring for several times.After completion of the reaction, Solvent was removed under vacuum to get crude material • The solid was treated with water under stirring and heating. Cool the rm and filter the solid. The crude solids are washed with water. Dry the product to give White to off white solid STAGE 2 • Charge Ethyl acetate and step 1 and in Reactor. Charge Benzene Sulfonic acid solution in ethyl acetate in above RM. Heat the mass. Heat the reaction mass under stirring for several time. • After completion of the reaction, Solvent was removed under vacuum to get crude material. The solid was treated with methanol under stirring and heating. Cool the rm and filter the solid. The crude solids are washed with methanol. Dry the product to give White to off white solid Chemical Reaction: Mass Balance: Sr. Input No. 1 Phthaloyl Amlodipine 2 Mono Methyl Amine 3 Methanol 4 Ethyl Acetate 5 Benzene Sulfonic Acid 6 Carbon 7 Water Total Quantity (Kg) Output Quantity (Kg) 1.09 1.68 4.38 3.09 0.38 0.75 8.80 Final Product Methanol Ethyl Acetate Residue Drying + Distillation loss Effluent Carbon waste 1.00 4.18 2.80 0.11 0.58 10.68 0.14 20.17 Total 20.17 43. NEBIVOLOL AND ITS INTERMEDIATE Manufacturing Process: PFA is condensed with Maleic anhydride in presence of AlCl3 and Dichloro ethane solvent to give NB-1. NB-1 is then cyclized to give NB-2. NB-2 is reduced to NB-3 using Palladium charcoal catalyst. NB-3 is reduced using sodium Borohydride to give NB-4. NB-4 is reduced to give NB-5. NB-5 is epoxydised using dimethyl sulphoxide in presence of MDC to give NB-6. NB-6 is condensed with Benzyl Amine in presence of Methanol to give NB-7. NB-7 is debenzoylated with Ammonium formate and palladium charcoal to give NB-8. NB-8 is then condensed with HCl to give Nebivilol Hydrochloride. Chemical Reaction: Mass Balance: Sr. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 Particular Maleic Anhydride AlCl3 EDC Para Fluoro Anisole HCl Hexane Acetic Acid Sulphuric Acid Pd/c Hyflow Sodium Borohydride THF MDC Sodium Carbonate DMSO Oxahl Chloride TEA Sodium Hydride Methanol Benzyl Amine Acetonitrile Water Total Input Qty (kg) 2.8 7.73 302.38 2.91 6.63 115.84 1.7 2.36 0.82 1.63 2.31 112.51 232.34 1.78 42.99 6.54 12.98 1.96 36.05 0.66 16.31 30.9 942.13 Sr. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Particular Product Effluent to ETP Spent Pd/c EDC Recovered EDC Loss Hexane Recovered Hexane Loss THF Recovered THF Loss MDC Recovered MDC Loss DMSO Recovered DMSO Loss Residue HCl 30% Total Output Qty (kg) 2.00 44.5 0.7 296.3 6.08 110.51 5.33 109.0 3.51 225.36 6.98 41.9 1.09 1 57.04 942.13 44. ETORICOXIB Manufacturing Process Ketosulfone is reacted with CPT-Phosphate in presence of Potassium tert-Butoxide in Tetra hydrofurane to give Etoricoxib crude .Etoricoxib crude recrystallized from IPA-Hexane to give Etoricoxib Chemical Reaction Stage-I: Preparation 2-chloro malonaldehyde from sodium salt of 2-chloromalonaldehyde Stage-II: Preparation 3-amino-2- chloroacrolien from 2-chloro-malonaldehyde Stage-III: Preparation of Etoricoxib hydrochloride Stage-IV: Preparation of Etoricoxib (API) Material Balance Sr. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Input Acetic Acid Acetone Ammonia Solution CPT-Phosphate D M Water Hydroxylamine Hydrochloride Hyflow Isopropyl Alcohol Ketosulfone Methanol Potassium Tertrabutoxide (KTB) Sodium Acetate Sodium Hydroxide Toluene THF Trifluro Acetic Acid Activated Carbon Hexane Total Qty (kg) 1.520 2.80 5.80 1.520 26.00 0.115 0.177 10.00 0.574 10.00 0.664 0.297 2.153 55.000 23.00 0.465 0.022 0.250 139.357 Output Etoricoxib Acetone Recovery Acetone Recovery Loss Isopropyl Alcohol Recovery Isopropyl Alcohol Recovery Loss Methanol Recovery Methanol Recovery Loss Toluene Recovery Toluene Recovery Loss Qty (kg) 1 2.657 0.124 9.500 0.450 9.65 0.35 53.5 1.25 Aqueous Effluent Spent Carbon Dist. Residue THF Recover THF Loss 37.054 0.022 0.5 22 0.8 Total 139.357 45. VALSARTAN Manufacturing Process There are following steps involved in the synthesis of Valsartan. Step - 1: - Preparation of L- METHYL VALINATE L- Valine is treated with methanol in presence of Thionyl chloride to get L- Valine methyl ester which was then neutralized with alkali solution to get L-methyl valinate. Step - 2: - Preparation of VALSARTAN OXALATE L- Methyl valinate is condensed with 4- bromo methyl -2 - cyano biphenyl in presence of potassium carbonate which was then treated with oxalic acid to isolate the Valsartan oxalate. Step - 3-A: - Preparation of VALEROYL VALSARTAN The Valsartan oxalate is condensed with Valeroyl chloride in presence of potassium, Carbonate in o- xylene to get Valeroyl Valsartan. Step - 3-B and 3-C: - Preparation of CRUDE VALSARTAN The cyano group of Valeroyl Valsartan is cyclized in presence of tri butyl tin chloride and sodium azide in oxylene at reflux to get methyl Valsartan. The methyl Valsartan is then hydrolyzed with sodium hydroxide and isolated with dichloromethane and cyclohexane to get crude Valsartan. Step - 4:- Preparation of VALSARTAN CALCIUM The crude Valsartan is treated with calcium hydroxide in acetone and D I water and filtered to obtained calcium salt of Valsartan. Step - 5- Preparation of VALSARTAN Valsartan calcium salt is treated with hydrochloric acid in ethyl acetate and water. The ethyl acetate layer is treated with diisopropyl ether to obtain the pure Valsartan. Chemical Reaction Material Balance 46. Tranexamic Acid Manufacturing Process: • In to an Auto clave charge 4-amino methyl benzoic acid. • Charge Aq. solution of Sodium hydroxide. • Charge ruthenium and apply hydrogen pressure. • Heat it and maintain it. • Filter the reaction mass and collect filtrate. • Charge Hydrochloric Acid to adjust pH. • Distill out water. • Charge methanol and water. • Maintain it. • Filter it. • Dry to give Tranexamic Acid. Chemical Reaction: Material Balance Sr. Input No. 1 4-aminomethyl benzoic Acid 2 HCl 3 Ruthenium Qty (kg) 1.060 Product Qty (kg) 1.000 0.440 0.300 Ruthenium Recover Methanol Recover 0.292 1.950 Sodium hydroxide Methanol Water Total 0.252 2.000 7.800 11.852 Loss Effluent Dist. Residue Total 0.050 8.51 0.050 11.852 4 5 6 Output 47. GUANYL THIOUREA Manufacturing Process: Charge water and dicynadiamide at room temperature. Charge phosphourous penta sulphide and sodium hydro sulphite at room temperature. heat it to 45 °c to 55 °c and maintain the temperature till reaction complite. Cool and centrifuge. Wet cake dry in dryer and pack. Mother liquor is di – potassium phosphate which is selling in liquid form. Chemical Reaction: NH H2N C N C H2N N + P2S5 H 2H3PO4 + KOH + H2O S C N C NH2 + 2H3PO4 + 4H2S + KOH + H2O HN H POTASSIUM SULPHATE Material Balance Sr. Input No. 1 Phosphorus Penta Sulphide 2 KOH 3 Dicyanadiamide Qty (kg) 182 220 200 Sodium Hydro Sulphite Water Total 40 300 942 4 5 Output Product Di Potassium Phosphate Drying Loss Qty (kg) 220 384 15 HCl Gas 323 Total 942 48. 1,3 DI CHLORO ACETONE Manufacturing Process: Stage-I Add Epichlorohydrin (500 kg) in Glass Line Reactor and cool to 0'C to 5"C 5"C.' Now addn 30% HCl(1200kg )within i0to12hrs 0to12hrs when temperature is between 0'C to 5"C' After this separate the 20% solution of Spent Hydrochloric Acid (Qty: 12) kg) and organic layer containing 1,3-Dichloro-2--Prolmnol (480.0 kg) Stage-II 480 kg) and Sodium Dichromate solution (1500 Now charge 1,3.Dichloro-2.Propanol (480 kg) 1 in Glass Line Reactor and Cool to 10"C - 18"C Then slowly add 70% solution of Sulphuric Acid (1000kg) within 10 to 15 hrs when temperature is 10"C to 18"C. After this add DM water (500 kg) g) and Cool to 10"C' Transfer reaction mass is centrifuge fuge to separate mother liquor containing 1 &12% solution of Basic chromium sulphate (3046 kg) and crude 1,3 Dichloroacetone (434 kg). Take crude 1,3-Dichloroacetone Dichloroacetone in Glass Line Reactor and heat to 50"c to separate lower layer containing product 1,3-Dichloroacetone Dichloroacetone (384 kg) and acidic waste water (50 kg)' Keep 1,3 Dichloroacetone in clean HDPE carboy and cool it to soc for 5-6 hrs for solidification. Chemical Reaction: Mass Balance: Sr. Input No. 1 Epichlorohydrin 2 HCl (30%) 3 Sulfuric Acid (98%) 4 5 Sodium Dichromate Water Total Qty (kg) 500 1200 715 600 1685 4700 Output Product Dil. HCl Basic Chromic Sulphate Qty (kg) 384 1220 3046 Effluent 50 Total 4700 49. FOLIC ACID Manufacturing Process: Step-I PABGA, TAPS and TCA are charged in to a reactor containing sufficient water and are stirred maintaining required pH. The technical folic acid formed is subjected to the next stage. Step-II The technical folic acid is treated with acid and is passed through filter press and the solid so obtained is taken for the next stage. Step-III The crude folic acid is dissolved in alkaline solution and is filtered through leaf filter. The folic acid filtrate is treated with acid and the solid so obtained is subjected to centrifugation. Chemical Reaction: o OH CH2 H CO2H N O + CO2H + C NH2 NH2 H CH2 H O O N CO2H N N NH2 H CO2H N N H N H NH2 N H2SO4 N NH2 Mass Balance: Sr. Input No. 1 PABGA 2 TAPS 3 TCA Qty (kg) 50 45 32 4 5 6 7 8 9 10 18 60 580 300 11 16 SMBS NaHCO3 water HCl 30% NaOH Acetic Acid Total 1112 Output Product Solid Waste Gas Emission Qty (kg) 50 93 45 Drying Loss Effluent 300 624 Total 1112 50. ZOLPIDIC ACID Manufacturing Process: Stage 01 Reactor is charged with toluene, 4-methylphenacyl bromide, 2-amino-5-methyl pyridine and tri ethyl amine and maintained at temp 15-20 0C for 6 hrs. After completion of the reaction, filter the mass, collect the solid cake and wash the solid with water. Obtain stage 01 product as wet cake which is dried to afford stage 01 product. Stage 02 Stage 01 product is reacted with, Oxaloyl chloride in presence of MDC as a solvent and TEA as a organic base at RT temp for 3hrs followed by addition of KOH solution. Then increase the temp of reaction mass up to 80 0C and simultaneously distill MDC. After complete removal of MDC cool the reaction mass to 60 0C and add hydrazine hydrate and reflux for 16 hrs. Cool the reaction mass and add KOH. Further increase temp up to 130 and remove water. Cool the reaction mass and filter; acidify the filtrate with acetic acid. Collect Crude Zolpidic acid and crystallize in methanol. Dry the product in hot air oven to afford Zolpidic acid. Chemical Reaction: 1. Route of Synthesis Stage – 1: Preparation of Stage 01 O Br H 3C + N + N N(C 2 H 5 ) 3 Toluene CH 3 N H 3C NH 2 + N(C 2 H 5 ) 3 . HBr H 2O 2 - Amino - 5 - methyl pyridine Triethyl amine 181.9 18 4 - Methyl Phenacyl bromide 2 - (4 - methylphenyl) - 6 - methyl imidazo[1,2 -a] - pyridine C 6 H 15 N C 6H 8N 2 C 9 H 9 BrO C 15 H 14 N 2 + CH 3 212.9 108 101 222 Stage – 2: Preparation of Zolpidic acid Cl O N MDC N ++ (C 2 H 5 )3 N 2 KOH N 2 x 56 H C H3C 3 Cl O 2 - (4 - methylphenyl) - 6 - methyl imidazo[1,2 -a] - pyridine CH3 C 15 H 14 N 2 O O Oxalyl chloride 101 C 2 Cl 2 O 2 222 CH3 N + 137.5 O C 17 H 13 KN 2 O 3 + KCl 74.5 332 N N CH 3 N + H 3C H 2N NH 2 CH 3 N H 3C O O O N K K H 2N O 32 CH 3 N + 2 KOH H 3C K 346 CH 3 N Methanol H 3C O 2 x 56 O C 17 H 15 KN 4 O 2 18 N N O H 2O 346 332 N + O C 17 H 15 KN 4 O 2 N 2H 4 C 17 H 13 KN 2 O 3 H2N 18 (C 2H 5) 3 N.HCl K 127 + H2O + 3 CH 3 COOH Acetic acid 3 x 60 OH C 17 H 16 N 2 O 2 Zolpidic acid 280 + N2 + 2 H 2O 28 2 x 18 3 CH 3 COOK 3 x 98 Mass Balance: Sr. No. Input QTY (Kg) Output QTY (Kg) Toluene 1750 Stage 01 350 350 Recovered toluene 1665 214 Aqueous effluent 1 2485 Step-I 1 2 3 Methyl Phenacyl bromide 2- Amino-5-methyl pyridine 4 Triethyl amine 186 Solvent loss 85 5 Water 2100 Distillation residue 15 4600 Total 4600 Total Step-II 1 Stage 01 350 Zolpidic acid 350 2 Oxalyl chloride 245 Recovered MDC 1680 3 Methylene Dichloride 2100 Recovered methanol 3150 4 Potassium hydroxide 469 Aqueous effluent 2 8423 5 Water 7000 Solvent loss 770 6 Acetic acid 578 Distillation residue 20 7 Hydrazine hydrate 151 8 Methanol 3500 Total 14393 Total 14393 51. PREGABALIN Manufacturing Process Sodium Hydroxide solution in Process water is chilled at 0-10°C and then charge R-(-)-3-(Carbamoylmethyl)5-methylhexanoic acid [R-(-)-CMH]. Addition of liquid Bromine is done at 0-5°C then raise the temperature of the reaction mass up to 30-35°C. After reaction monitoring, raise the temperature of the reaction mass to 55-60°C and apply carbon treatment. The clear filtrate is then received in another reactor. Excess water is distilled off from the reaction mass. The reaction mixture is acidified with concentrated Hydrochloric acid. Reaction mass is then up to 80-85°C and after that gradual cooling to 25-30°C. The material is centrifuged after maintaining of the reaction mass at 25-30°C for 4-6 hrs. The dry material is then charged in IPA and raises the temperature to 80-85°C. Add DM water to reaction mass at 80-85°C. Filter the clear reaction mass and chill it to 8-12°C. The material is then centrifuged and dried in under vacuum. Chemical Reaction Material Balance Stage - 1 Sr. No. 1 Raw Material Process water Sodium Hydroxide 4-CMH Liquid Bromine Activated carbon Hyflo Hydrochloric acid Total 2 3 4 5 6 7 Quantity Kgs 2590.0 347.2 250.0 224.0 12.5 3.0 450.0 3877 Out Put Quantity Kgs Spent carbon and hyflo Spent ML Loss on drying Out Put Total 28.0 3623.7 62.5 162.5 3877 Stage - 2 Sr. No. 1 2 3 Raw Material Pregabalin (Stage-I) IPA DM water Total Quantity Kgs 215.0 1290.0 860.0 2365 Out Put Spent ML Loss o Drying Out Put Total Quantity Kgs 2150.00 32.2 182.8 2365 ANNEXURE-4 WATER CONSUMPTION AND WASTE WATER GENERATION (EXISTING AND PROPOSED) Sr. Usage Water Consumption (m3/Day) No. Existing 1. Waste Water Generation (m3/Day) Total after Existing Total after proposed proposed expansion expansion Industrial Process 2.43 30 2.95 24.0 Boiler 2.5 15 0.25 0.5 Cooling 3.0 15 Nil 0.5 Washing 3.0 5.0 3.0 5.0 10.93 65.0 6.2 30.0 Total (Industrial) 2. Domestic 1.0 2.0 1.0 2.0 3. Gardening -- 5.0 -- -- 11.93 72.0 7.2 32.0 Total Note: Existing: • Domestic effluent is disposed though septic tank & soak pit system. • Industrial effluent is collected in effluent collection tank and finally sent to CETP of ETL for final treatment and disposal. Proposed: • Domestic effluent will be disposed though septic tank & soak pit system. • Industrial effluent (low COD = 25 KL/day) will be given primary treatment and then sent to CETP of M/s. ETL for treatment and disposal. Industrial effluent (high COD = 5 KL/day) will be given primary treatment and then sent to common MEE of M/s. ETL for treatment and disposal. WATER BALANCE DIAGRAM Raw Water: 72 KL/Day from GIDC Domestic 2 KL/Day 2 KL/Day Soak Pit & Septic tank Process 30 KL/Day 24 KL/Day Cooling Tower 15 KL/Day 0.5 KL/Day Boiler 15 KL/Day 0.5 KL/Day ETP: 30 KL/Day (Low COD + High COD Stream) Final treated effluent to CETP for further Treatment Washing 5 KL/Day 5 KL/Day Gardening 5 KL/Day Annexure -5 Effluent Treatment Plant (ETP) DETAILS: Existing: M/s. Hem-Deep Organics Pvt. Ltd. has two (02 nos.) collection tank for high COD and Low COD effluent stream. Raw effluent from plant separates as high COD and Low COD stream and collects in concern collection tank where it neutralizes and get settles. Neutralized high COD effluent then sends to common MEE facility of M/s. ETL, Ankleshwar for further treatment and final disposal whereas low COD sends to CETP operates by M/s. ETL, Ankleshwar for further treatment and final disposal. ETP Units Name & Size: Sr. No. Unit Name 1 Collection Tank-1 2 Collection Tank-2 3 Collection Tank-3 Size (m x m x m) 4.5 x 2.5 x 4.0 10.0 KL 10.0 KL Proposed: Stream I (Low COD & TDS Stream) First all non-toxic and biodegradable streams (low & medium COD& TDS) of wastewater shall pass through Screen Chamber (SC-01) where floating material shall be removed with help of Screen (S-01). Then effluent shall be passed through Oil & Grease Removal Tank (OGRT-01). Automatic mechanical Oil Skimmer shall be provided in the OGRT to remove floating oil and grease from the wastewater to Oil & Grease Collection Tank (OGCT-01). Then effluent shall be collected in Collection cum Equalization tank-1 (CET-01). Pipe grid is provided at bottom of the CET-01 to keep all suspended solids in suspension and to provide proper mixing. 2 nos. of Air Blowers (1W+1 stand-by) shall supply air through to pipe grid. Then after, equalized wastewater shall be pumped to Neutralization Tank-1 (NT-01) where the continuous addition and stirring of Caustic solution is done to maintain neutral pH of wastewater from Caustic Dosing Tanks (CDT-01) as per requirement by gravity. Then after, neutralized wastewater shall go to Flash Mixer-1 (FM-01) by gravity. Alum and Polyelectrolyte shall be dosed from Alum Dosing Tank (ADT-01) and Polyelectrolyte Dosing Tank (PEDT-01) respectively by gravity into FM-1 to carry out coagulation by using a Flash Mixer. Then after, coagulated wastewater shall be settled in Primary Clarifier (PCF-01).Treated effluent will be sent to CETP for further treatment. SIZE OF TANKS (Stream I): 25 KL/day S.N. Name of unit No . MOC/ Remark Stream I (Low COD & TDS Stream) 1 Screen Chamber (SC-01) [0.6x0.5x1 depth] 1 RCC M25+A/A Bk. Lining 2 1 RCC M25+A/A Bk. Lining Collection cum Equalization Tank-1 (CET-01) Size (m x m x m) [2.5x2.5x 6 depth] 3 4 5 Neutralization Tank (NT-01) Flash Mixer-1 (FM-01) Primary Clarifier (PCL-01) RCC M25 PCC PP MSEP SS = = = = = [2.5x2.5x 6 depth] 1.5 x 1.5 x (2.0 LD +1.0 FB) [2.5x2.5x 6 Height] REINFORCED CEMENT CONCRETE (M 25 GRADE) PLAIN CEMENT CONCRETE POLYPROPELENE MILD STEEL EPOXY PAINTED STAINLESS STEEL 1 1 RCC M25+A/A Bk. Lining RCC M25 1 RCC M25 BLOCK DIAGRAM FOR EFFLUENT TREATMENT PLANT (Stream -I) Screen Chamber Oil & Grease Trap Collection cum equalization tank Neutralization tank Primary Settling tank CETP EXPECTED CHARACTERISTIC OF EFFLUENT (STREAM-I) Sr. No. Category of Wastewater Before Treatment After Treatment 1 pH 3.5-6.5 6.5-8.5 2 COD (mg/L) 3,200 2,500 3 BOD3 (mg/L) 1,250 800 4 Ammonical Nitrogen (mg/L) 50 40 EXPECTED CHARACTERISTIC OF EFFLUENT (STREAM-II) Sr. No. Category of Wastewater Before Treatment 1 pH 2-10 2 COD (mg/L) 55,000 3 BOD3 (mg/L) 12,000 4 TDS (mg/L) 40,000 5 Ammonical Nitrogen (mg/L) 200 Stream-2: High COD & High TDS: 5 KL/day High COD & High TDS effluent will be neutralized in tank and neutralized effluent will be sent to common MEE for further treatment & disposal. ANNEXURE: 6 DETAILS OF HAZARDOUS/SOLID WASTE GENERATION, MANAGEMENT AND DISPOSAL Sr. Hazardous/Solid Category Quantity Mode Of Disposal No. Waste Existing Total after proposed expansion 1 Discarded HDPE 33.1 200 Nos./ Year 1000 Collection, Storage, Drums/Bags (4 MT/Year) Transportation and sell to Nos./Month Register Re-processors after decontamination. 2 Used / Spent Oil 5.1 5.0 Lit/Year 10 Lit/Month Collection, Storage, Transportation and sell to registered recycler. Collection, Storage, Transportation 3 ETP Sludge 35.3 -5 MT/Month 4 Distillation Residue 28.1 750 Kg/ Month 10 MT/Month 5 Spent Carbon 28.2 150 Kg/ Month 2 MT/Month 6 HCL 30 % C15 2.0 MT/Month 7 Spent Catalyst 28.3 -- 100 MT/Month 2 MT/Month 8 Inorganic Salt 28.1 -- 20 MT/Month 9 Organic Waste 28.1 -- 25 MT/Month Process and sent to common TSDF of M/s. BEIL. Collection, Storage, Transportation and sent for co-processing in cement industries or sent to common incineration at BEIL. Collection, Storage, Transportation and sent for co-processing in cement industries or sent to common incineration at BEIL. Collection, Storage, Transportation and sell to end user. Collection, Transportation regenerator and Storage, sent to Collection, Storage, Transportation and sent to common TSDF at BEIL. Collection, Storage, Transportation and sent for co-processing in cement industries or sent to common incineration at BEIL. ANNEXURE: 7 DETAILS OF FLUE & PROCESS GAS EMISSION AND CONTROL MEASURES Sr. No. Source Emission of Existing 1 Non IBR Boiler (Capacity: 0.6TPH) 2 Process (Reactor) Vent Stack/Vent (meter) Height Diameter Fuel name & Quantity use Type of Emission APCE SPM SO2 NOx -- SO2 HCl HBr Two Stage Alkali scrubber SPM SO2 NOx SPM SO2 NOx SPM SO2 NOx -- 12 0.1 10 0.1 Natural Gas = 10 Sm3/Day or LDO = 500 Lit/Day -- 0.2 Natural Gas = Total Proposed TOTAL PROPOSED EXPANSION Flue Gas Emission 1 Boiler (Existing) 15.0 (Capacity: 0.6TPH) 3 300 Sm /Day 2 Boiler (Proposed) (Capacity: 2.0 TPH) 30 0.5 Agro waste = 8 MT/Day 3 Thermic fluid heater (Proposed) (Capacity: 4 Lakh KCal/Hr.) D. G. Set 30 0.5 Agro waste – 2 MT/Day 11 0.1 HSD SPM SO2 NOx -- 11 0.2 -- Two Stage Water & Caustic scrubber 11 0.2 -- Cl2 NH3 HCl HCl SO2 4 Process Gas Emission 5 Process Vent (Reactor Vessel) (Existing) 6 Process Vent (Reactor Vessel) (Proposed) Multicyclone separator with bag filter Multicyclone separator with bag filter Two Stage Water & Caustic scrubber ANNEXURE: 8 DETAILS HAZARDOUS CHEMICAL STORAGE FACILITY Sr. No. Name of the Hazardous Substance Maximum Storage Mode of Storage Actual Storage 1 Methanol 20 MT Tank 20 MT x 1 State & Operating pressure & temperature NTP Possible type of Hazards 2 EDC/MDC 20 MT Tank 20 MT x 1 NTP 3 DMF 10 MT Tank 20 MT x 1 NTP 4 Toluene 20 MT Tank 20 MT x 1 NTP Flammable/ Toxic Flammable/ Toxic Flammable/ Toxic Flammable 5 Acetone 20 MT Tank 20 MT x 1 NTP Flammable 6 Ethyl Acetate 20 MT Tank 20 MT x 1 NTP Flammable 7 IPA 20 MT Tank 20 MT x 1 NTP Flammable 8 HCL 5 MT Tank 5 MT x 1 NTP Corrosive 9 H2SO4 5 MT Tank 5 MT x 1 NTP Corrosive ANNEXURE 9 SOCIO - ECONOMIC IMPACTS 1) EMPLOYMENT OPPORTUNITIES The manpower requirement for the proposed project is expected to generate some permanent jobs and secondary jobs for the operation and maintenance of plant. This will increase direct / indirect employment opportunities and ancillary business development to some extent for the local population. This phase is expected to create a beneficial impact on the local socio-economic environment. 2) INDUSTRIES Required raw materials and skilled and unskilled laborers will be utilized maximum from the local area. The increasing industrial activity will boost the commercial and economical status of the locality, to some extent. 3) PUBLIC HEALTH The company regularly examines, inspects and tests its emission from sources to make sure that the emission is below the permissible limit. Hence, there will not be any significant change in the status of sanitation and the community health of the area, as sufficient measures have been taken and proposed under the EMP. 4) TRANSPORTATION AND COMMUNICATION Since the existing factory is having proper linkage for the transport and communication, the development of this project will not cause any additional impact. In brief, as a result of the proposed project there will be no adverse impact on sanitation, communication and community health, as sufficient measures have been proposed to be taken under the EMP. The proposed project is not expected to make any significant change in the existing status of the socio - economic environment of this region. ANNEXURE – 10 PROPOSED DRAFT TERMS OF REFERENCE 1. • • • • • • • • • • Project Description Justification of project. Promoters and their back ground Project site location along with site map of 5 km area and site details providing industries, surface water bodies, forests etc. Project cost Project location and Plant layout. Water source and utilization including proposed water balance. Product spectrum (proposed products along with production capacity) and process List of hazardous chemicals. Mass balance of each product Storage and Transportation of raw materials and products. various 2. Description of the Environment and Baseline Data Collection • Micrometeorological data for wind speed, direction, temperature, humidity and rainfall in 5 km area. • Existing environmental status Vis a Vis air, water, noise, soil in 5 km area from the project site. For SPM, RSPM, SO2, NOx. • Ground water quality at 5 locations within 5 km. • Complete water balance 3. Socio Economic Data • Existing socio-economic status, land use pattern and infrastructure facilities available in the study area were surveyed. 4. Impacts Identification And Mitigatory Measures • Identification of impacting activities from the proposed project during construction and operational phase. • Impact on air and mitigation measures including green belt • Impact on water environment and mitigation measures • Soil pollution source and mitigation measures • Noise generation and control. • Solid waste quantification and disposal. 5. • • • Environmental Management Plan Details of pollution control measures Environment management team Proposed schedule for environmental monitoring including post project 6. • • • Risk Assessment Objectives and methodology of risk assessment Details on storage facilities Process safety, transportation, fire fighting systems, safety features and emergency capabilities to be adopted. • Identification of hazards • Consequence analysis through occurrence & evaluation of incidents • Disaster Management Plan. 7. Information for Control of Fugitive Emissions 8. Post Project Monitoring Plan for Air, Water, Soil and Noise. 9. Information on Rain Water Harvesting 10. Green Belt Development plan ANNEXURE – 11 GIDC Plot Transfer Letter & GIDC Water Supply Letter ANNEXURE – 12 Membership Certificate of CETP, ETL-Ankleshwar for disposal of treated effluent ANNEXURE – 13 Membership Certificate of TSDF & Common Incinerator for disposal of Hazardous waste