3-氯头孢烯酸的合成

以3 羟基 7 苯乙酰基 3 头孢烯酸二苯甲酯为原料,经过氯代、酯水解、酰胺水解3步反应制备了药物头孢克洛的中间体3 氯头孢烯酸(7 氨基 3 氯 3 头孢烯 4 酸,7 ACCA),总收率73%。酶解反应中以c(NaHCO3)=1×10-3mol/L的水溶液代替常用的氨水溶液,缩短了反应时间。三氯化磷作为氯代试剂,间甲酚作为酯水解试剂,反应中采用TLC进行终控,展开剂分别为V(环己烷)∶V(乙醇)=1∶1和V(丙酮)∶V(石油醚)∶V(乙酸)=5∶5∶1。

Synthesis of 3-Chlorocephalosporin

3-Chlorocephalosporin (7-amino-3-chloro-3-cephem-4-carboxylic acid,7-ACCA) as the advanced intermediate of cefaclor was synthesized in high yield started with diphenylmethyl ester of 3-hydroxy-7-phenylaceto-3-cephem-4-carboxylic acid through three-step process including chlorination,hydrolysis of the ester and hydrolysis of the amide.The total yield was 73%.In the process of enzymatic hydrolysis of the amide,c(NaHCO_3)=1×10~(-3) mol/L aqueous solution was used instead of aqueous ammonia to shorten the reaction time.Phosphorus trichloride was used as chlorinating agent and m-cresol was used as hydrolytic agent of the ester.In the process of chlorination and ester hydrolysis,TLC was adopted for end point control,using V(cyclohexane)∶V(ethanol)=1∶1 and V(acetone)∶V(petroleum ether)∶V(acetic acid)=5∶5∶1 as the developing agent respectively.