头孢克洛中间体7-氨基-3-氯-3-头孢烯-4-酸的合成工艺研究  

Study on synthetic process of 7-amino-3-chloro-3-cephem-4-carboxylic acid,an intermediate of cefaclor

作　　者：李晶[1] 沈方烈[1] 郑昀红[1] LI Jing;SHEN Fang-lie;ZHENG Yun-hong(Zhejiang Research Institute of Chemical Industry Co.,Ltd.,Hangzhou 310023,China)

机构地区：[1]浙江省化工研究院有限公司,浙江杭州310023

出　　处：《中国药物化学杂志》2021年第6期426-430,共5页Chinese Journal of Medicinal Chemistry

摘　　要：目的优化7-氨基-3-氯-3-头孢烯-4-酸的合成工艺。方法以青霉素G钾盐为起始原料,经酯化氧化、开环重排、氧化、闭环、氯化脱酰基、酯水解共6步反应合成头孢克洛中间体7-氨基-3-氯-3-头孢烯-4-酸。结果与结论目标产物的结构经1H-NMR谱确证,总收率为38%(以青霉素G钾盐计),纯度达99.4%(HPLC法)。该工艺步骤较短、操作简单、易于分离纯化、收率更高,适合工业化生产。7-Amino-3-chloro-3-cephem-4-carboxylic acid(7-ACCA)was an important intermediate of cefaclor.In this study,7-ACCA was synthesized from penicillin G patassium salt via six-step reaction,including esterification and oxidation,rearrangement reaction,oxidation,cyclization,chlorination and deacylation,and deesterification.The total yield of the final product was 38%with the purity of 99.4%(HPLC).This optimized process is suitable for the industrial production.

关 键 词：头孢克洛 中间体 7-氨基-3-氯-3-头孢烯-4-酸 合成工艺 

分 类 号：R914[医药卫生—药物化学]