Process for preparing of monohydrate and crystal modifications of fluconazole

摘要

The process for preparing of monohydrate and crystal modifications of fluconazole of formula (I), comprising: a) hydrolyzing a silyl ether derivative of the general formula (II) at a pH preferably either below 3 or above 8 in an aqueous solution, cooling the obtained reaction mixture containing the fluconazole and isolating the precipitated fluconazole monohydrate, and optionally dissolving the fluconazole monohydrate obtained from the hydrolysis of silyl-fluconazole in a C1-C4 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 C1-C4 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 at 30-70 °C, to obtain the crystal modification II of fluconazole, or d); drying fast fluconazole monohydrate at 80 °C, to obtain the crystal modification I of fluconazole.