METHOD FOR PREPARING CRYSTALLINE FORM II OF (1R,5R,6S)-P-NITROBENZYL-2-DIPHENYLPHOSPHORYLOXY)-6-[(R)-1-HYDROXYETHYL]-1-METHYL-CARBAPENEM-3-CARBOXYLATE

摘要

PURPOSE: A method for preparing (1R, 5R, 6S)-p-nitrobenzyl-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapenem-3-carboylate(MAP) crystalline II is provided to obtain MAP crystalline II of high purity and high yield without separate cooling process. CONSTITUTION: A method for preparing (1R, 5R, 6S)-p-nitrobenzyl-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapenem-3-carboylate(MAP) crystalline II comprises: a step of dissolving (1R, 5R, 6S)-p-nitrobenzyl-2-(diphenylphosphoryloxy)-6-[(R)-1-hydroxyethyl]-1-methyl-carbapenem-3-carboylate(MAP) crystalline I in dichloromethane, chloroform, or acetone; and a step of crystallizing by dropping diethyl ether, isopropyl ether, normal hexane, normal heptanes, or cyclo hexane. The dichloromethane or chloroform is used in a volume of 2-10 times to MAP weight. The acetone is used in a volume of 2-10 times to MAP weight. The MAP crystalline I is dissolved in dichloromethane or chloroform at 5-60°C or in acetone at 30-60°C.