第 45 卷第 1 期 Vol. 45 No. 1 2015 年 2 月 Feb 2015

所属栏目：医药及中间体 头孢他啶侧链活性酯中一个未知杂质的合成和确认

厉 昆1，李啸风2，任红阳1，江海波1 （1. 浙江普洛得邦制药有限公司，浙江 东阳 322118；2. 浙江大学 化学系，浙江 杭州 310027）

摘　要：对合成头孢他啶产生的杂质头孢他啶甲酯进行了测定和推测，并对原料他啶侧链活性酯（TAEM）进行了追踪分析，发现TAEM中有个未知杂质，经LC-MS和HPLC测定，证实这个杂质的产生跟TAEM与甲醇溶媒有关系。据此合成了一个化合物，其结构经LC-MS和HPLC确证。

关键词：头孢他啶；他啶侧链活性酯；头孢他啶甲酯

中图分类号：R978.1　　文献标识码：A　　文章编号：1009-9212（2015）01-0057-04

Synthesis and Confirmation of an Unknown Impurity in(Z)-2-S-Benzothiazoly-2-(2-aminothiazol-4-yl)-2-(1-methoxy-2-methyl-1-oxopropan-2-yloxyimino)acetic Acid Ester

LI Kun1, LI Xiao-feng2, REN Hong-yang1, JIANG Hai-bo1 (1. Zhejiang Apeloa Tospo Pharm Co., Ltd., Dongyang 322118, China; 2. Department of Chemistry; Zhejiang University, Hangzhou 310027, China)

Abstract：The impurity(ceftazidime methyl)produced in the synthesis of ceftazidime were analyzed and speculated, and 2-Mercaptobenzothiazolyl-(Z)-(2-aminothiazol-4-yl)-2-(tert-butoxycarbonyl)isopropoxyiminoacetate(TAEM), a raw material for the synthesis of ceftazidime, was analyzed. The analytical results indicated that an unknown impurity existed in TAEM, and the experimental results from LC-MS and HPLC determination indicated that the existence of the impurity was related to a reaction between TAEM and methanol solvent. Based on the above deduction, a compound with the same molecular weight from LC-MS analysis and same retention time in HPLC analysis of the unknown impurity in TAEM was synthesized.

Key words：ceftazidine; TAEM; ceftazidine methyl

作者简介： 厉 昆（1974-），男，浙江东阳人，高级工程师，硕士研究生，主要从事医药中间体和药物合成研究（E-mail：kun.li@apeloa.com）。

收稿日期：2014-11-24