摘要
目的探索制备普拉格雷合成重要中间体2-氟-α-环丙酰苄基溴的较优工艺条件。方法以邻氟溴苄为原料,经格氏反应和环丙基腈作用生成环丙基-2-氟苄基酮,再经α位溴化得到2-氟-α-环丙酰苄基溴。结果最佳配比为镁∶邻氟溴苄∶环丙基腈=1.1∶1∶0.8(摩尔比),洗脱液为石油醚∶乙酸乙酯=20∶1和15∶1(体积比),α-位溴化时用氢溴酸和过氧化氢代替液溴。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 synthesize the α-cyclopropylcarbonyl-2-fluorobenzyl bromide, which is an important intermediate for the synthesis of prasugrel, the optimum reaction conditions were explored by experiments. Methods Cyclopropyl 2-fluorobenzyl ketone was prepared starting from 2-fluorobenzyl bromide through Grignard reaction with eyelopropaneearbonitrile. Then α-cyclopropylcarbonyl-2-fluorobenzyl bromide was synthesized by the α-H of cyclopropyl 2-fluorobenzyl ketone being substituted by the atom of Br. Results The optimized matching conditions were Mg: 2-fluorobenzyl bromide: cyclopropanecarbonitrile = 1.1 : 1 : 0. 8 and the eluent was ligroin: acetic ether = 20:1 and 15: 1. The bromine,which was used for the substitution of α-H by the atom of Br was replaced by hydrobromic acid and hydrogen peroxide. Conclusions The upgraded process was rational and feasible, which could be used as experimental basis for mass production.
出处
《广东药学院学报》
CAS
2009年第3期272-274,共3页
Academic Journal of Guangdong College of Pharmacy