摘要
目的改进利伐沙班关键中间体4-(4-氨基苯基)-3-吗琳酮(Ⅰ)的合成方法。方法将溴苯(Ⅱ)先硝化再与乙醇胺反应后依次经氯乙酰化、还原得到2-[2-氯-N-(4-氨基苯基)乙酰胺基]乙基2-氯乙酸酯(Ⅵ);中间体Ⅵ在碱性条件下环合制得Ⅰ;或经叔丁氧羰基保护、环合,再在浓盐酸作用下脱除叔丁氧羰基保护基制得Ⅰ。结果目标化合物的结构经1HNMR确证,上述两种方法的总收率分别为26.6%、19.0%。结论所用方法具有反应步骤少、原料易得、条件温和、操作简便、收率较高等优点。
OBJECTIVE To improve the method for the synthesis of 4 - （4 - aminophenyl） - 3 - morpholinone （ Ⅰ ）. METHODS Bromobenzene （ Ⅱ ） underwent a sequence of reactions of nitration, N- arylation, acylation, reduction and cyclization, and yielded that 2 - [ N - （4 - aminobenzene） - 2 - chloroacetamido ] ethyl - 2 - chloroacetate （ Ⅵ）. Compound I was prepared from intermediate VI via cyclization under alkdine condition. Or from di - t - butyl dicarbonate protected Ⅵ via cyclization, and then deproteetion of tert - butyloxy - carbonyl group in the presence of concentrated hydrochloric acid. RESULTS The chemical structure of 4 - （4 - aminophe- nyl） -3 -morpholinone was determined bylHNMR. The overall yields of these two methods were about 26. 6% and 19.0%, respectively. CONCLUSION The method has the advantages of fewer reaction steps materials obtained easily, milder reaction condi- tion, easier operation and higher yield.
出处
《华西药学杂志》
CAS
CSCD
2015年第6期642-644,共3页
West China Journal of Pharmaceutical Sciences
