3-N-叔丁氧羰基胺基环丁胺的便捷合成  

Convenient Synthesis of 3-N-Tert-butoxycarbonyl Aminocyclic Butylamine

作　　者：段志芳 王婷 沈洁 陈金妹 吴翠婷 曾鹏 DUAN Zhi-fang;WANG Ting;SHEN Jie;CHEN Jin-mei;WU Cui-ting;ZENG Peng(School of Food and Pharmaceutical Engineering,Zhaoqing University,Zhaoqing 526061,China;College of Pharmacy,Jinan University,Guangzhou 510632,China)

机构地区：[1]肇庆学院食品与制药工程学院,广东肇庆526061 [2]暨南大学药学院,广东广州510632

出　　处：《安徽化工》2020年第1期32-35,41,共5页Anhui Chemical Industry

基　　金：2018年肇庆学院大创项目(201810580023);肇庆市科技项目(2018NN019);肇庆学院实践教改项目(sjjx201818);肇庆学院博士启动项目

摘　　要：以N-二苯甲基氮杂环丁烷-3-醇为起始原料,经酰化、取代、Boc保护、催化氢化四步反应得到3-N-叔丁氧羰基胺基环丁胺,总产率约为72%。最终产物结构经NMR、MS、HPLC表征,并研究了酰化反应中反应温度对1-二苯甲基-3-甲烷磺酸氮杂环丁烷收率的影响,系统考查了催化氢化反应的影响因素,得出较佳工艺条件为:酰化反应温度0℃;还原反应中,m(Pd/C)∶m(III)=1∶20,反应温度为60℃,氢气压力为0.8~1.1 MPa。该合成路线的优点为反应路线较短,总收率较高,反应条件温和,原料试剂廉价易得,路线便捷,“三废”可控,产品质量稳定,具有工业化大规模生产的潜力。3-N-Tert-butoxycarbonyl aminocyclic butylamine was synthesized from N-diphenylmethyl azacyclobutane-3-alcohol by a four steps process of acylation,substitution,boc protection and catalytic hydrogenation.The total yield was about 72%.The structure of the final product was confirmed by NMR,MS and HPLC.The effect of reaction temperature on the yield of 1-diphenylmethyl-3-methanesulfonate azacyclic butane was studied.The influencing factors of catalytic hydrogenation were systematically investigated.The optimum process conditions were obtained as follows:acylation temperature 0℃and reduction reaction,m(Pd/C)∶m(III)=1∶20,reaction temperature 60℃and hydrogen pressure 0.8~1.1 MPa.The advantages of this synthetic route are short reaction route,high total yield,low cost and easy availability of reaction conditions and raw material reagents,mild reaction conditions,convenient route,controllable waste,stable product quality,and potential for large-scale industrial production.

关 键 词：3-N-叔丁氧羰基胺基环丁胺 氮杂环 药物中间体 钯碳还原 

分 类 号：TQ460.1[化学工程—制药化工]