摘要
报道一种从L-乳酸出发拆分制备巴尼地平关键中间体(R)-1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-5-甲氧羰基-3-吡啶羧酸的合成新方法,即以L-乳酸为起始原料,经硫酸催化异丙酯化、2,2,6-三甲基-4H-1,3-二噁英-4-酮乙酰乙酰化后与3-氨基巴豆酸甲酯、间硝基苯甲醛进行Hantzsch反应,然后用乙醇重结晶拆分得到(S)-1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-5-甲氧羰基-3-吡啶羧酸-(S)-1-异丙氧基-1-氧代-2-丙醇酯,后者经碱水解、酸化得到目标产物,总收率20.6%,纯度98.66%,结构经1H NMR、HRMS鉴定。
A novel method was reported for the resolution of(R)-2,6-dimethyl-4-(3-nitrophenyl)-5-(methoxycarbonyl)-1,4-dihydropyridine-3-carboxylic acid,the key intermediate of barnidipine.L-lactic acid was used as starting material via isopropylation,acetoacetylation,Hantzsch reaction and resolution to obtain(S)-3-((S)-1-isopropoxy-1-oxopropan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-5-(methoxycarbonyl)-1,4-dihydropyridine-3-carboxylate.Subsequently,the target product was obtained by hydrolysis and acidification with a total yield of 20.6%and a purity of 98.66%.The chemical structure was confirmed by 1H NMR and HRMS.
作者
王建塔
张吉泉
毛远湖
汤磊
WANG Jian-ta;ZHANG Ji-quan;MAO Yuan-hu;TANG Lei(Guizhou Medical University,Guizhou Guiyang 550004;Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D,Guizhou Guiyang 550004,China)
出处
《广州化工》
CAS
2019年第22期53-55,共3页
GuangZhou Chemical Industry
基金
贵州省研究生教育教学改革重点课题(黔教合YJSCXJH[2018]019)
贵州省科技计划社会攻关项目(黔科合[2016]支撑2851)
贵阳市科技计划项目(筑科合同[20161001]41号)
贵州省普通高等学校科技拔尖人才支持计划(黔教合KY字[2017]072)
关键词
巴尼地平
关键中间体
L-乳酸
拆分
barnidipine
key intermediate
L-lactic acid
resolution
作者简介
第一作者:王建塔(1981-),男,正高级实验师,从事化学药物合成工艺研究;通讯作者:汤磊,博士,教授,博士生导师,主要从事化学药物研究。
