特立氟胺合成方法的工艺改进  

Technological improvement of teriflunomide synthesis method

作　　者：王磊 王有宪 李瑛光[1] 张伟[1] 徐士伟 郭庆明[1] WANG Lei;WANG You-xian;LI Ying-guang;ZHANG Wei;XU Shi-wei;GUO Qing-ming(Jiangsu Kangyuan Pharmaceutical Co.,Ltd.,Lianyungang 222000,China)

机构地区：[1]江苏康缘药业股份有限公司,江苏连云港222000

出　　处：《化学研究与应用》2022年第12期2995-2999,共5页Chemical Research and Application

摘　　要：以对三氟甲基苯胺为起始原料,在缩合剂EDC的作用下直接与氰乙酸缩合得到关键中间体2-氰基-N-(4-(三氟甲基)苯基)乙酰胺。经甲醇钠脱质子,与乙酰氯发生取代、重排反应得特立氟胺成品。中间体和成品结构均经(1)^H NMR、(13)^C NMR和HR-MS(ESI)确证。通过工艺优化,产品收率大幅度提高。该方法原料廉价易得、反应条件温和、操作安全性高、绿色环保,具有广阔的工业化前景。Taking p-trifluoromethylaniline as the starting material,it was directly condensed with cyanoacetic acid under the action of the condensing agent EDC to obtain the key intermediate compound 2-cyano-N-(4-(trifluoromethyl)phenyl)acetamide.After deprotonation with sodium methoxide,substitution and rearrangement reactions with acetyl chloride occured to obtain the finished product of teriflunomide.The intermediate and finished structures were confirmed by(1)^H NMR,(13)^C NMR and HR-MS(ESI).Through process optimization,the product yield was greatly improved.The method had cheap and easy-to-obtain raw materials,mild reaction conditions,high operational safety,green environmental protection,and had broad industrialization prospects.

关 键 词：特立氟胺 2-氰基-N-(4-(三氟甲基)苯基)乙酰胺 EDC 合成 工艺优化 

分 类 号：O623.626[理学—有机化学]