1-甲基-3-(哌啶-4-基)脲盐酸盐的合成  

Synthesis of 1-methyl-3-(piperidin-4-yl)urea hydrochloride

作　　者：王艳娇[1,2] 李衍松 刘斌 唐文强[1,2] WANG Yan-jiao;LI Yan-song;LIU Bin;TANG Wen-qiang(School of Pharmacy,Shaanxi Institute of International Trade&Commeree,Xi'an 712046,China;Collaborative Innovation Center of Green Manufacturing Technology for Traditional Chinese Medicine in Shaanxi Province,Xi'an 712046,China)

机构地区：[1]陕西国际商贸学院医药学院,陕西西安712046 [2]陕西省中药绿色制造技术协同创新中心,陕西西安712046

出　　处：《精细与专用化学品》2020年第11期40-43,共4页Fine and Specialty Chemicals

基　　金：陕西省中药绿色制造技术协同创新中心一般培育项目(2019XT-3-09);陕西国际商贸学院2020年科学研究项目(SMXY202018);2020年国家级大学生创新创业训练计划项目(S202013123006)。

摘　　要：以4-氨基哌啶-1-羧酸叔丁酯和甲氨基甲酰氯为原料,通过N-酰基化反应、脱Boc保护两步反应合成得到目标化合物1-甲基-3-(哌啶-4-基)脲盐酸盐,两步反应总收率为70.5%(以4-氨基哌啶-1-羧酸叔丁酯计算)。产物结构经~1H-NMR和ESI-MS表征。重点研究了N-酰基化反应,确定其最佳反应条件为:n(甲氨基甲酰氯)∶n(4-氨基哌啶-1-羧酸叔丁酯)=1.1∶1,n(K2CO3)∶n(4-氨基哌啶-1-羧酸叔丁酯)=2.5∶1,反应温度为25℃时,反应时间为4h。1-Methyl-3-(piperidin-4-yl)urea hydrochloride was synthesized from tert-butyl 4-aminopiperidine-1-carboxylate and methylcarbamic chloride through a two-step reaction in a total yield of 70.5%(take tert-butyl 4-aminopiperidine-1-carboxylate as the basis),involving N-acylation reaction and Boc-group deprotection.The structure of the product was confirmed by 1H-NMR and ESI-MS.The optimal reaction conditions of N-acylation reaction were also investigated,and the optimal conditions on the yield of tert-butyl 4-(3-methylureido)piperidine-1-carboxylate were as follows:the mole ratio of n(methylcarbamic chloride)∶n(tert-butyl 4-aminopiperidine-1-carboxylate)=1.1∶1.The amount of K2CO3 is n(K2CO3)∶n(tert-butyl 4-aminopiperidine-1-carboxylate)=2.5∶1,the reaction was at 25℃for 4 h.

关 键 词：哌啶衍生物 脲类化合物 脱保护基 合成 

分 类 号：TQ463[化学工程—制药化工]