氯沙坦合成工艺改造

Technical Optimization of the Synthesis of Losartan

以2-正丁基-4-氯-1H咪唑-5-甲酰基和对溴苄溴为原料,合成氯沙坦。其间经过烷基化,得到重要中间体2-正丁基-4-氯-1-[4-溴-苯甲基]-1H咪唑-5-甲酰基,再经取代的硼酸偶联、脱保护、硼氢化钠还原得到氯沙坦。此合成路线较为简便。

Losartan was synthesized with 2-butyl-4-chloro-5-formylimidazole and 4-bromobenzyl bromide as starting material to obtain the most important intermediate 2-butyl-4-chloro-[4-bromobenzyl]-5-formylimidazole by alkylation,followed by coupling with 2-[（N-triphenylmethyl）tetrazol-5-yl]phenyl boronic acid,then by deprotection,finally by reduction with sodium borohydride.The proposed method was optimal for the synthesis of losartan.