普拉格雷中间体的合成工艺改进

An Improved Method for Synthesizing Prasugrel Intermediate

目的对普拉格雷中间体2-溴-2-(2-氟苯基)-1-环丙基乙酮的合成工艺进行改进优化。方法以邻氟溴苄为起始原料制得的格式试剂与环丙基氰反应生成2-(2-氟苯基)-1-环丙基乙酮,再经二溴海因光照反应4h,制得抗血栓药物普拉格雷重要中间体2-溴-2-(2-氟苯基)-1-环丙基乙酮。结果该工艺采用二氯甲烷为溶剂,过氧化苯甲酰为反应促进剂,制得产物含量达到96%,产率为83.9%。结论改进后的合成方法工艺合理、可行,为工业化生产提供了实验依据。

Objective To improve and optimize the synthetic method of prasugrel intermediate 2-bromo-2-（2-fluorophenyl）-l-cyclopropylethanone. Methods A Grignard reagent, prepared by 2-fluorobenzyl bromide,was added into cyclopropanecarbonitrile to produce cyclopropyl 2-fluoro- benzyl ketone,which was then illuminated with 1,3-dibromo-5,5-dimethylhydantoin for 4 hours. The resulting product was evidenced to be 2-bromo-2-（2-fluorophenyl）-l-cyclopropylethanone. Results Methylene chloride was used as a solvent and benzoyl peroxide as a reaction accelerator. The content of the obtained product was 96 M. The productivity was 83.9 %. Conclusion The im-proved synthetic method is reasonable and feasible for the industrial production of 2-Bromo-2-（2-fluorophenyl）-l-cyclopropylethanone.