7α-甲氧头孢菌素关键中间体7-MAC的合成

化工进展

7α-甲氧头孢菌素关键中间体7-MAC的合成

赵德明，李敏，蔡丽霞，张建庭，金宁人

浙江工业大学化学工程与材料学院，浙江杭州 310032

出版日期:2010-10-05 发布日期:2010-10-05

Synthesis of key intermediate 7-MAC for 7α-methoxycephalosporins

ZHAO Deming，LI Min，CAI Lixia，ZHANG Jianting，JIN Ningren

College of Chemical Engineering and Materials Science，Zhejiang University of Technology，Hangzhou 310032，Zhejiang，China

Online:2010-10-05 Published:2010-10-05

摘要/Abstract

摘要：

以7-氨基-（1-甲基-1H-四唑-5-硫甲基）-3-头孢烯-4-羧酸二苯甲酯（7-DAMC）为原料经缩合和甲氧基化等一系列反应制备得到甲氧头孢关键中间体7β-氨基-7α-甲氧基-3-（1-甲基-1H-四唑-5-硫甲基）-3-头孢烯-4-羧酸二苯甲酯（7-MAC）。实验结果表明合成中间体7-对甲苯硫亚氨基-3-（1-甲基-1H-四唑-5-硫甲基）-3-头孢烯-4-羧基酸二苯甲酯（7-DTMC）的较佳条件为：n(7-DAMC)∶n(TSC)∶n(环氧丙烷)=1∶3.5∶40，反应时间为3 h，反应温度为30 ℃；产品7-MAC的较佳合成条件为：n(甲醇)∶n(无水AlCl₃)∶n(PPh₃)∶n(7-DTMC)=230∶1.5∶2∶1，反应温度25 ℃，PPh₃插入反应时间15 h，甲氧基化反应时间5 h，收率54.17%，HPLC纯度99.15%。产品结构均经¹H-NMR和IR表征认证。

Abstract:

7α-Methoxy-7β-amino-3-[（1-methyl-1-H-tetrazo-5-yl）thiomethyl]-3-cephem-4-carboxylic acid diphenylmethyl ester（7-MAC）was synthesized through condensation and methoxylation reactions from 7β-amino-3-[（1-methyl-1-H-tetrazo-5-yl）thiomethyl]-3-cephem-4-carboxylate（7-DAMC），4-tolysulfenyl chloride（TSC）and methanol. Proper experimental conditions for diphenylmethyl 7-(4- tolysulfenylimino)-3-[(1-methyl-1H-tetrazo-5-yl)thiomethyl]-3-cephem-4-carboxylate (7-DTMC) were found as n(7-DAMC)∶n(TSC)∶n(propylene epoxide)=1∶3.5∶40 with 3 h of reaction at 30 ℃. The optimal methoxylation reaction conditions were found as n(methanol)∶n(anhydrous AlCl₃)∶n(PPh₃)∶n(7-DTMC)=230∶1.5∶2∶1 with total 20 h of reaction at 25 ℃. The yield of 7-DTMC was 87.11% based on 7-DAMC and the purity was 99.21%，and the yield of 7-MAC based on 7-DTMC was 54.17% and the purity was 99.15% as determined by HPLC. The molecular structure of 7-DTMC and 7-MAC were exactly identified by ¹H-NMR and FT-IR.

赵德明，李敏，蔡丽霞，张建庭，金宁人. 7α-甲氧头孢菌素关键中间体7-MAC的合成 [J]. 化工进展.

ZHAO Deming，LI Min，CAI Lixia，ZHANG Jianting，JIN Ningren. Synthesis of key intermediate 7-MAC for 7α-methoxycephalosporins[J]. Chemical Industry and Engineering Progree.