高校化学工程学报Issue(3)：606-611,6.DOI:10.3969/j.issn.1003-9015.2014.03.027
（1R,2R）-2-（（R）-3-（苄氧基）吡咯烷基）环己醇的合成研究
Study on the Synthesis of (1R,2R)-2-((R)-3-(Benzyloxy)Pyrrolidin-1-yl)Cyclohexanol
叶海伟 1俞传明 1钟为慧 1苏为科1
作者信息
- 1. 绿色制药技术与装备教育部重点实验室，浙江工业大学 药学院，浙江 杭州 310014
- 折叠
摘要
Abstract
An improved synthetic technology was developed for the preparation of (1R,2R)-2-((R)-3-(benzyloxy)pyrrolidin-1-yl)cyclohexanol (RRR-2) which is a key intermediate in the synthesis of Vernakalant (1). (R)-3-Hydroxypyrrolidine (3) was used as the raw material that first went through an amino group selective protection and deprotection reaction, which was then followed by a ring-opening reaction with epoxy cyclohexane to prepare diastereoisomer-2. The target compound RRR-2 (optical pure) were obtained after separation with a total yield of 38% (literatures yield was 15%). Moreover, the isomer SSR-2 recovered from reaction liquids was further studied. SSR-2 was reacted via SN2 substitution with PPh3Cl2/TEA (molar ratio=1:2.1:2.5) under acetonitrile reflux, and followed by hydrolysis to prepare the diastereoisomer-2 with 75%yield. The structures of the intermediates and the product were confirmed by NMR, MS and chiral HPLC. The advantages of the present procedure include mild reaction condition, satisfactory yields, easy operation and reusability of the isomer SSR-2. Therefore it may be promising for industrial application.关键词
心房颤动/维纳卡兰/(1R,2R)-2-((R)-3-(苄氧基)吡咯烷基)环己醇/外消旋化Key words
atrial fibrillation (AF)/Vernakalant/(1R,2R)-2-((R)-3-(benzyloxy)pyrrolidin -1-yl)cyclohexanol/racemization分类
化学化工引用本文复制引用
叶海伟,俞传明,钟为慧,苏为科..（1R,2R）-2-（（R）-3-（苄氧基）吡咯烷基）环己醇的合成研究[J].高校化学工程学报,2014,(3):606-611,6.
