双溴代法合成奥卡西平
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摘要
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 ammonitication 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.
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 ammonitication 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.
引文
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[3]谢建伟,苏为科,周兆良.奥卡西平合成路线图解[J]:中国医药工业杂志,2005,36(2):123—125.
[4]张胜建,应丽艳,张洪.奥卡西平及其中间体的合成方法:中国,100999497A[P].2007-07-18.
[5]刘旭桃,李梅连,肖方青.奥卡西平的合成[J].中国医药工业杂志,2006,37(7):443—445.
[6]胡伟,谢建伟,蒋祖林,等.抗癫痫药物奥卡西平的合成[J].化工生产与技术,2010,14(4):35—37.
[7]苏为科,李坚军,蒋祖林,等.一种奥卡西平的化学合成方法:中国,101314590A[P].2008-12-03.
[8]胡卫雅.BTC参与的亚氨基芪的合成研究[D].杭州:浙江大学硕士学位论文,2008.