卡托普利中间体的制备工艺改进

摘要

An improved synthetic process of captopril intermediate,D-3-acetylthio-2-methylpropanoyl-L-proline,was carried out using potassium hydroxide and potassium dihydrogen phosphate buffer as a condensating agent.Add potassium dihydrogen phosphate into a raw material of the L-proline,then,drop potassium hydroxide to form potassium hydroxide and potassium dihydrogen phosphate buffer as a condensating agent,the title compound was synthesized by dropping another raw material of 3-acetylthio-2-methyl-propanoyl chloride into above prepared solution.The pH of reaction system keeps in from 7.5 to 8.5,the reaction process is simple and efficient, and the average yield of product was improved from 33% to 39.5%.%使用磷酸氢二钾-氢氧化钾缓冲溶液作为缩合剂,对卡托普利关键中间体D-3-乙酰硫基-2-甲基丙酰-L-脯氨酸的制备工艺进行了改进.反应过程中,加入磷酸氢二钾至L-脯氨酸中,滴加氢氧化钾溶液作缩合剂,形成磷酸氢二钾-氢氧化钾缓冲溶液,然后与3-乙酰硫基-2-甲基丙酰氯缩合,制得标题产物.反应溶液的pH值很容易保持在7.5～8.5,反应平稳,操作简便,产品平均收率由33%提高到39.5%.