甲氧头孢菌素中间体7-AMCA的合成工艺优化

7β-氨基-3-（1-甲基-1H-四唑-5-硫甲基）-3-头孢烯-4-羧酸（7-AMCA）是合成甲氧头孢菌素关键中间体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）的重要中间体。采用7-氨基头孢霉烷酸（7-ACA）和1-甲基-1H-1，2，3，4-四唑-5-硫醇（5-MMT）为原料，以乙酸为溶剂，甲磺酸为催化剂，经亲核取代制备得到7-AMCA。本文主要探讨了物料配比、催化剂用量、反应时间和温度等因素对反应的影响，并通过二次回归建立了数学模型，确定了合成7-AMCA的最佳工艺条件。在此基础上合成的产品收率高达93．24％，HPLC纯度98．76％。产品结构经^1H NMR和IR表征确认。

Optimization of Preparing Methoxycephalosporins Intermediate 7-AMACA

7 - Amino - 3 - （ 1 - Methyl - 1 - H - tetrazo - 5 - yl） thiomethyl ] - 3 - cephem - 4 - carboxylie acid （ 7 - AMCA） is the important intermediates for the synthesis of 7 α - Methoxy - 7β - Amino - 3 - （ 1 - Methyl - 1 - H - tetrazo - 5 - yl） thiomethyl ] - 3 - cephem - 4 - carboxylic acid diphenylmethyl ester （7 - MAC ） and 7 - MAC is the key intermediate for preapring 7α - methoxycephalosporins. 7β - Amino - 3 - （ 1 - Methyl - 1 - H - tetrazo - 5 - yl ） thiomethyl ] - 3 - cephem - 4 - carboxylic acid （ 7 - AMCA） was synthesized by using 7 - Aminocephalosporanic acid （ 7 - ACA） and 5 - mercapto- 1 -methyl- 1,2,3,4 -tetrazole （5 -MMT） as the materials, the acetic acid used as the solvent, the methylsulfonic acid as the catalyst. The main four influential factors of nucleophilic substitution reaction such as the molar ratio, the amount of catalysis, the reactiontime and temperature were studied. By using orthogonal quadratic regression design, the mathematic model was established and the optimization experimental conditions were obtained. The yield of 7 - AMCA was 93.24 % on this basis of 7 - ACA, the purity of HPLC was 98.76 %, and its molecular structure was exactly identified by ^1H- NM, R and FT- IR.