Patent ID: 7094904

Claim:
A process for the synthesis of monohydrate and crystal modifications of fluconazole of formula (I) comprising the steps of: a.) hydrolyzing a silyl ether derivative of formula (II) wherein the meaning of R 2 is hydrogen, or a C 1 –C 10 alkyl or phenyl group, R 3 and R 4 independently of each other are a C 1 –C 10 alkyl or phenyl group—at a pH preferably either below 3 or above 8 in an aqueous solution, then cooling the obtained reaction mixture containing the fluconazole of formula (I) and isolating the precipitated fluconazole monohydrate and optionally dissolving the fluconazole monohydrate obtained from the hydrolysis of silyl-fluconazole in a C 1 –C 4 straight or branched chain alcohol at boiling temperature and cooling the solution with a speed of 5–15° C./h to obtain the crystal modification II of fluconazole, or b.) dissolving anhydrous fluconazole or monohydrate of it in a C 1 –C 4 straight or branched chain alcohol at boiling temperature and cooling the solution with a speed of 5–15° C./h to obtain the crystal modification II of fluconazole, or c.) drying slowly fluconazole monohydrate after seeding preferably with seeding crystals of crystal modification II at 30–70° 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° C., to obtain the crystal modification I of fluconazole.