摘要
对LCZ696的关键中间体(R)-叔丁基(1-([1,1′-联苯]-4-基)-3-羟基丙烷-2-基)氨基甲酸酯进行了工艺改进研究,即以价廉易得的甘氨酸甲酯盐酸盐为起始物料,经缩合、N-烷基化、水解、生物酶拆分、Boc酸酐保护、还原获得目标产物,反应总收率37.0%。
The method for the preparation of （R）-tert-butyl （1-（[1,1＇-biphenyl]-4-yl）-3-hydroxypropan-2-yl） carbamate, a key intermediate for LCZ696, was improved. The target product was synthesized from glycinemethylester hydrochloride via condensation, N-alkylation, hydrolysis, enzymatic resolution, Boc protection and reduction, and an overall yield of 37.0% was obtained.
作者
丛日刚
沈文丽
刘庆春
CONG Ri-gang SHEN Wen-li LIU Qing-chun(Disha Pharmaceutical Group Co., Ltd., Weihai 264205, Chin)
出处
《精细化工中间体》
CAS
2016年第5期22-24,共3页
Fine Chemical Intermediates
