摘要
本研究改进了N-甲基-2-(2-氨乙基)吡咯烷的合成工艺。以N-甲基吡咯烷酮和氰乙酸甲酯为主要原料反应得到2-氰基-2-(1-甲基吡咯烷-2-亚甲基)乙酸甲酯(5)。改用水替代甲醇为结晶溶剂,保证收率及质量的同时,降低了成本。2-氰基-2-(1-甲基吡咯烷-2-亚甲基)乙酸甲酯(5)在脱羧剂的作用下得到2-(1-甲基-2-吡咯烷基亚基)乙腈(6)。改用6 mol·L-1盐酸替代对甲苯磺酸作为脱羧剂,反应时间由48 h缩短至1 h,同时将产品纯度由67%提升至93%。2-(1-甲基-2-吡咯烷基亚基)乙腈(6)在雷尼镍的作用下氢化还原得到N-甲基-2-(2-氨乙基)吡咯烷(1)。改用甲醇作为反应溶剂,降低氢化反应压力,有效地降低偶合杂质的产生。改进后的工艺,成本低,条件温和,总收率为46.2%,纯度为99.0%。目标产物采用核磁共振进行了结构表征。
The synthesis of N-methyl-2-(2-aminoethyl)pyrrolidine was improved.N-methylpyrrolidone reacted with methyl cyanoacetate to obtain methyl 2-cyano-2-(1-methylpyrrolidine-2-methylene)acetate(5).In this step,water was used instead of methanol as the crystallization solvent to reduce the cost.Under the action of decarboxylating agent,2-Cyano-2-(1-methylpyrrolidine-2-methylene)acetate methyl ester(5)gave 2-(1-methyl-2-pyrrolidinylidene)acetonitrile(6).6 mol·L-1hydrochloric acid was used instead of p-Toluenesulfonic acid to short the reaction time,and the purity could increase from 67%to 93%.2-(1-methyl-2-pyrrolidinylidene)acetonitrile(6)gave N-methyl-2-(2-aminoethyl)pyrrolidine(1)by catalytic hydrogenation.The methanol was as a solvent and the pressure was reduced to reduce the coupled impurity.The improved process had low cost,mild conditions,a total yield of 46.2%,and a purity of 99.0%.The structure of the title compound was characterized by 1H NMR,and 13C NMR.
作者
林波
章玉华
张峰强
张正兵
Lin Bo;Zhang Yuhua;Zhang Fengqiang;Zhang Zhengbing(Zhejiang Hisoar Chuannan Pharmaceutical Co., Ltd., Zhejiang Linhai 317000)
出处
《化工时刊》
CAS
2020年第4期6-8,16,共4页
Chemical Industry Times
