PROCESS FOR PREPARING FLUCONASOLE AND ITS CRYSTAL MODIFICATIONS

摘要

The invention relates to a process for preparing of fluconazole of formula and its crystal modifications. The process is as follows: a) hydrolyzing a silyl ether derivative of formula wherein the meaning of R2 is hydrogen, or a C1-C10 alkyl or phenyl group, R3 and R4 independently of each other are a C1-C10 alkyl or phenyl group, at a pH preferably either below 3 or above 8 in an aqueous solution, cooling the obtained reaction mixture and isolating the precipitated fluconazole monohydrate, dissolving the fluconazole monohydrate in a C1-C4 straight or branched chain alcohol at boiling temperature and cooling the solution slowly, preferably with a speed of 5-15 degrees C/h to obtain the crystal modification II of fluconazole, or fast, preferably with speed of 35-65 degrees C/h to obtain the crystal modification I of fluconazole and in both cases isolating the precipitated crystals and drying, or b) dissolving fluconazole monohydrate in C1-C4 straight or branched chain alcohol at boiling temperature and cooling the solution slowly, preferably with a speed of 5-15 degrees C/h to obtain the crystal modification II of fluconazole, or fast, preferably with a speed of 35-65 degrees C/h to obtain the crystal modification of fluconazole and in both cases isolating the precipitated crystals and drying, or c) drying slowly fluconazole monohydrate after seeding preferably with seeding crystals of crystal modification II at 30-70 degrees C, preferably in vacuum to obtain the crystal modification II of fluconazole, or d) drying fast fluconazole monohydrate after seeding preferably with seeding crystals of crystal modification I at 80 degrees C, to obtain the crystal modification I of fluconazole. 10 claims, 6 figures