Ⅰ型氯吡格雷硫酸氢盐的合成工艺改进

Improved preparation method of crystalline form Ⅰ of clopidogrel hydrogen sulfate

目的优化Ⅰ型氯吡格雷硫酸氢盐的合成工艺。方法以(R)-(-)-邻氯扁桃酸为原料,经甲酯化、磺酰化和亲核取代反应合成氯吡格雷,最后与浓硫酸反应生成氯吡格雷硫酸氢盐。结果新合成方法操作更加简便,总收率为58.3%。结论改进后的工艺便于纯化,更适应于工业化生产。

Objective To optimize the preparation of crystalline form Ⅰ clopidogrel hydrogen sulfate.Methods Clopidogrel was synthesized by esterification of the starting material 2-chloromandelic acid,and subsequent sulfonylation and nucleophilic substitution.Then the clopidogrel hydrogen sulfate was prepared by treatment with concentrated sulphuric acid.Results The total yield of clopidogrel hydrogen sulfate by the improved method was 58.3 %,and the operation was more convenient.Conclusion The improved synthesis process is convenient and cost-saving,and more suitable for industrial production.