100 kg class
Production of pharmaceutical grade crystals.
Reagents
1. Raw materials and dosage
Reagents
2-Bromo-4-methylpropiophenone (2b4mp) Reaction starting material 110 kg Purity > 98%
Methylamine solution (40%) Methylamine aqueous solution (or hydrochloride form) 45-50 kg Maintain a moderate excess to prevent incomplete reaction
Dichloromethane (DCM) Reaction and crystallization main solvent 500-600 liters Distillation purification, drying and water removal
Acetone or isopropanol Anti-solvent (for crystallization stage) 200-300 liters Anhydrous grade is preferred
Deionized water For washing and extraction 300 liters Low ion content
Anhydrous sodium sulfate Dry organic phase 5-10 kg Industrial grade or analytical grade
Activated carbon (optional) Decolorization and removal of impurities 1-2 kg For hot filtration treatment
Equipment
Reactor (200L or larger, with stirring and condensing reflux device) Material: glass lining or stainless steel
, equipped with temperature control system, vacuum interface, nitrogen protection interface cooling circulation device (-10°C to 50°C temperature control), used to accurately control the reaction temperature and cooling crystallization process, centrifuge or Buchner filter device (industrial grade), used for solid-liquid separation, collecting crystals, vacuum dryer, temperature control range: 30-50°C, ensure low solvent residue, solvent recovery device (rotary evaporator or distillation tower)
Operation steps
Dissolve 110 kg of 2-bromo-4-methylacetophenone in 200 liters of dichloromethane (DCM), start stirring and heat to 25-30°C. , add methylamine dropwise, slowly add 45-50 kg of methylamine solution (40%), control the dripping speed, and keep the reaction temperature at 20-30°C. The temperature is critical at this stage and should not exceed 30°C to prevent side reactions. Time control: 4-6 hours, ensure uniform dropwise addition and complete reaction. Monitor the progress of the reaction to confirm that the raw materials have been basically exhausted. After the reaction is completed, let it stand and cool to 20°C, add an equal amount of **deionized water (200-300 liters)** to separate the layers. Wash with deionized water 3 times until the pH is close to neutral. Dry the organic layer with anhydrous sodium sulfate, stir for 30 minutes and filter to obtain a dry DCM solution. Heat the dry DCM solution to 40°C to ensure that the target product is completely dissolved. If the solution is dark in color, add activated carbon (1-2 kg) and stir for 30 minutes, then filter hot to remove impurities and pigments. Slowly cool to room temperature (20-25°C) and stir for 30 minutes. Continue to cool the solution to 0-5°C and keep for 1 hour. The crystals will gradually transfer the crystals to a vacuum dryer, set the temperature to 40°C, and dry for 6-8 hours until the solvent residue is less than 0.5%.
Separate and recycle the solvent
The recovered mother liquor is filtered through a coarse filter to remove solid impurities or crystal residues to prevent clogging of the distillation system. The mother liquor is poured into the distillation kettle, and the filling amount is 70-80% of the total capacity of the kettle to prevent overflow or excessive foaming. Atmospheric or reduced pressure distillation, the temperature is controlled at 40-45°C, and the pressure is set at 30-50 mbar (reduced pressure state) to prevent the decomposition of dichloromethane. The steam is cooled into liquid through the condenser and enters the receiving tank. The cooling water temperature is maintained at 0-5°C to improve the condensation efficiency. Re-distillation (optional): For solvents that are used multiple times, secondary distillation can be performed to improve the purity. The cost of recovering dichloromethane is only 10-20% of the new purchase cost. The purity of the solvent after recovery meets the requirements of reaction and crystallization
I declare again that I do not sell precursors. Many people communicate with me on the session. I do not sell any precursors. Any transaction that violates the custody system is 99.99% a scam. Many people also ask me what my purpose is. I only tell you that I look down on this kind of small business. I can only tell you that if you arrive in China legally one day, I will take you to visit the company. I am engaged in a completely legal business. Thank you again for the trust and support of the BB Forum. I hope that the BB Forum will get better and better.
Salute to you and the forum administrators
