甲氧头孢中间体7-MAC的合成工艺改进

Improvement to the synthesis of methoxy cephalosporin's intermediate 7-MAC

以7-ACA为原料制备7β-氨基-3-(1-甲基-1H-四唑-5-硫甲基)-3-头孢烯-4-羧酸,并以二苯甲酮为原料经过两步反应制备二苯重氮甲烷,然后再经过二苯甲基保护、缩合、氧化、加成以及取代等5步反应制备了标题化合物。通过核磁共振氢谱确证其化学结构,总收率为32.3%(以7-ACA为基准)。该方法原料易得,操作简单,收率稳定,具有工业化的价值。

This article is related to the procedure for synthesis of 7-MAC in commercial scale. The intermediate 7β-amine-3-[5- （ 1-methyl-1, 2, 3, 4-tetrazolyl ）-thiomethyl ]-A3-cephem-4-carboxylate was prepared from 7-ACA, while another intermediate diazodiphenylmethane was prepared from benzophenone via a two-step process. After reactions involving protection by diphenylmethyl group, condensation, oxidation, addition and substitution, to form the target compound-diphenylmethyl 7β-amine-7α-methoxy- 3- [ 5- （ 1- methyl- 1,2,3,4- tetrazolyl ）- thiomethyl ]- △^3- cephem-4- carboxylate（7-MAC）, which was the key intermediate of methoxy cephalosporin. Chemical structures of the target product were verified by ^1HNMR. The total yield of the target product was 32.3 % （using calculations based on 7-ACA）. This synthesis procedure with readily available starting materials and easily controllable operation and stable yield is worthy of the pilot manufacture.