双溴代法合成奥卡西平

Synthesis of Oxcarbazepine via Dibromination

本研究设计以下新路线合成奥卡西平(1)。10,11-二氢-5H-二苯并[b,f]氮杂(2)与三光气反应得10,11-二氢-5H-二苯并[b,f]氮杂-5-甲酰氯(3),3经"一锅法"先与二溴海因在自由基引发剂过氧化苯甲酰作用下进行双溴代反应,再高温脱溴化氢制得10-溴-5H-二苯并[b,f]氮杂-5-甲酰氯(5),再经氨水氨化、稀盐酸水解得1,总收率39%(以2计),纯度99.6%。该法中3经双溴代-脱溴化氢得5的方法未见文献报道。

A new synthetic route for oxcarbazepine（1） was reported. 10,11-Dihydro-5H-dibenzo[b,f]azepine（2）reacted with bis（trichloromethyl）carbonate in chlorobenzene to give 10,11-dihydro-5H-dibenzo[b,f]azepine-5-carbonyl chloride（3） with a yield of 81% . Then compound 3 was subjected to dibromination with dibromohydantoin and benzoyl peroxide in chlorobenzene, and then dehydrobromination at 140 ℃ to afford 10-bromo-5H-dibenzo[b,f]azepine-5-carbonyl chloride（5）, which was followed by ammonification with ammonia and hydrolysis with diluted hydrochloric acid to prepare the target compound with a purity of 99.6% and a total yield of 39% （based on compound 2）. The synthetic method of 5 from 3 has not yet been reported in literatures.