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3h,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15h,甲氧基化反应时间5h,收率54.17%,HPLC纯度99.15%。产品结构均经1H-NMR和IR表征认证。
7α-Methoxy-7β-amino-3-[(1-methyl-1-H-tetrazo-5-yl)thiomethyl]-3-cephem-4-carboxylic acid diphenylmethyl este(r7-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.
出处
《化工进展》
EI
CAS
CSCD
北大核心
2010年第10期1969-1974,共6页
Chemical Industry and Engineering Progress
基金
浙江省教育厅科研项目(20060798)
浙江工业大学校基金重点项目(20070174)