雷芬那辛的合成工艺研究  

Study on Synthesis Process of Revefenacin

作　　者：陈年根[1] 林景美 钟霞[1] CHEN Nian-gen;LIN Mei-jing;ZHONG Xia(School of Pharmacy,Hainan Medical University,Hainan Haikou 571199;Hainan Women and Children's Medical Center,Hainan Haikou 570206,China)

机构地区：[1]海南医学院药学院,海南海口571199 [2]海南省妇女儿童医学中心,海南海口570206

出　　处：《广州化工》2022年第7期78-81,共4页GuangZhou Chemical Industry

摘　　要：以联苯-2-基氨基甲酸哌啶-4-基酯(SM-1)为起始物料,经亲核取代、脱苄基、和4-甲酰基苯甲酸脱水反应生成酰胺中间体,最后和哌啶-4-甲酰胺脱水反应先形成希夫氏碱再经三乙酰氧基硼氢化钠还原制备雷芬那辛。通过对反应条件的控制及纯化,所得产品纯度为99.5%,总收率为45.7%,目标产物的化学结构经质谱和核磁共振确证。该工艺反应条件温和、操作简便,为雷芬那辛的合成提供了一种新选择。Revefenacin was synthesized from piperidin-4-yl[1,1′-biphenyl]-2-ylcarbamate(SM-1) as raw matercial via the nucleophilic substitution, removing the benzyl on nitrogen by Pd/C,reacting with p-formylbenzoic acid to dehydrate to form amide compound, dehydrating with piperidine-4-formamide to form schiff base and reducting by sodium triacetoxyborohydride etc. Through the control of the reaction conditions and purification of the intermediate and API,the purity of the product obtained was 99.5%,and the total yield was 45.7%. The chemical structures were confirmed by MS and;H-NMR and;C-NMR. The process was simple and a new choice for production of Revefenacin.

关 键 词：雷芬那辛 慢性阻塞性肺疾病 合成工艺 

分 类 号：R914[医药卫生—药物化学]