METHOD FOR SYNTHESIS OF FLUCONAZOLE MONOHYDRATE, METHOD FOR SYNTHESIS OF CRYSTALLINE MODIFICATION II OF FLUCONAZOLE (VARIANTS) AND METHOD FOR SYNTHESIS OF CRYSTALLINE MODIFICATION I OF FLUCONAZOLE Russian patent published in 2005 - IPC

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention describes a method for synthesis of fluconazole monohydrate of the formula (I): . Method involves hydrolysis of silyl ester derivative of the formula (II): wherein R² means hydrogen atom, (C₁-C₁₀)-alkyl or phenyl group; R³ and R⁴ mean independently of one another (C₁-C₁₀)-alkyl or phenyl group at pH value below 3 or above 8 in an aqueous solution followed by cooling the prepared reaction mixture and isolation of the precipitated fluconazole monohydrate. Also, invention describes methods for synthesis of crystalline modification II of fluconazole of the formula (I). These methods involve dissolving anhydrous fluconazole or its monohydrate in (C₁-C₄)-alcohol of the linear or branched chain at the boiling point and cooling this solution at the rate 5-15°C/h, or fluconazole monohydrate is dried at 30-70°C. Except for, invention describes a method for synthesis of crystalline modification I of fluconazole of the formula (I) wherein fluconazole monohydrate is dried at 80°C. This invention provides preparing pure or easily purifying fluconazole in crystalline modifications allowing easy preparing the suitable medicinal formulations from them.

EFFECT: improved synthesis method.

16 cl, 1 tbl, 7 dwg, 8 ex