Recrystallization process of flutamide

Abstract

The invention discloses a recrystallization process of flutamide. The recrystallization process of the flutamide comprises the following steps: adding medicinal ethanol or medicinal ethanol and petroleum ether into a reaction kettle with a stirring machine, a thermometer and a dropping funnel, adding flutamide crude products and active carbon under stirring, heating, stirring and refluxing, and filtering and distilling to remove active carbon when still hot to obtain distillate; placing the distillate into a beaker, stirring, slowly adding distilled water or petroleum ether into the beaker at a certain temperature by using the dropping funnel, stopping adding the distilled water or the petroleum ether when slightly mixing, and adding ethanol into the beaker dropwise by using a dropper until the solution is clear; performing sealed refrigeration until 3 to 7 DEG C and taking out, adding flutamide seed crystals with the purity being more than 99.3%, separating out yellowish needle-shaped crystals slowly, and slightly stirring for several times by using a clean glass rod; continuously performing refrigeration at 0 DEG C for 3 hours; and distilling to take crystals and drying at 60 DEG C for 8 hours, wherein melting point is 110 to 113 DEG C and purity is more than 99%. Benzene or methylbenzene is replaced by solvents such as ethanol and petroleum ether, so the deadlock that the flutamide is difficult to recrystallize is broken and harmful components of the flutamide products are reduced.

Description

technical field [0001] The invention relates to a recrystallization process of flutamide, which belongs to the technical field of chemical synthesis process. Background technique [0002] At present, there are pharmaceutical manufacturers with GMP certificates in my country. At present, the production route of flutamide is generally adopted: (1) first acylation to produce m-isobutyramide trifluorotoluene; (2) followed by mixed acid of sulfuric acid and nitric acid The crude product of flutamide can be obtained by nitration; the qualified product can be obtained by recrystallization from benzene or toluene. The residual amount of benzene or toluene is generally controlled below 100ppm. According to (Chinese Pharmacopoeia II, 1995 Edition, Appendix VIII P Residual Solvent Determination Method), the residual amount of benzene or toluene should not exceed 0.01%. If benzene or toluene is used for recrystallization, the residual amount should be less than 0.01%. Ethanol or other s...

AI Technical Summary

Problems solved by technology

The operation is cumbersome, the amount of solvent used is large, and the cost is high

According to the provisions of (Appendix VIII P Residual Solvent Determination Method of Chinese Pharmacopoeia II, 2010 Edition), benzene has been included in the list of avoidance, and its residual amount shall not exceed 0.0002%, so benzene or toluene cannot be used at all in the current actual production process