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[1]陈楚珺,冯瑾瑾,张 勤,等.阿拉莫林中间体的合成及表征[J].武汉工程大学学报,2018,40(03):243-249.[doi:10. 3969/j. issn. 1674?2869. 2018. 03. 002]
 CHEN Chujun,FENG Jinjin,ZHANG Qin,et al.Synthesis and Characterization of Anamorelin Intermediate[J].Journal of Wuhan Institute of Technology,2018,40(03):243-249.[doi:10. 3969/j. issn. 1674?2869. 2018. 03. 002]
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阿拉莫林中间体的合成及表征(/HTML)
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《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]

卷:
40
期数:
2018年03期
页码:
243-249
栏目:
化学与化学工程
出版日期:
2018-06-26

文章信息/Info

Title:
Synthesis and Characterization of Anamorelin Intermediate
文章编号:
20180302
作者:
陈楚珺1冯瑾瑾2张 勤2祁诗伟2黄齐茂*2
1. 武汉工程大学化学与环境工程学院,湖北 武汉 430205;2. 武汉工程大学化工与制药学院,湖北 武汉430205
Author(s):
CHEN Chujun1FENG Jinjin2ZHANG Qin2QI Shiwei2HUANG Qimao*2
School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan 430205, China ;2. School of Chemical Engneering and Pharmacy, Wuhan Institute of Technology, Wuhan 430205, China
关键词:
阿拉莫林 中间体合成 手性拆分 工艺优化
Keywords:
anamorelin intermediate synthesis chiral separation process optimization
分类号:
TQ460.31
DOI:
10. 3969/j. issn. 1674?2869. 2018. 03. 002
文献标志码:
A
摘要:
以3-哌啶甲酸和乙醇为原料酯化生成3-哌啶甲酸乙酯,在碱性条件下与二碳酸二叔丁酯加成,经氢氧化锂水合物水解得到1-叔丁氧羰基-3-苄基-3-甲酸哌啶,通过R-(+)-α-甲基苄胺的手性拆分得目标产物,利用核磁共振氢谱和质谱对其结构进行了表征。并对催化剂及合成工艺进行了优化,结果表明,碳酸钠催化效率最高;1-叔丁氧羰基-3-苄基-3-甲酸乙酯哌啶、氢氧化锂水合物和乙醇的投料质量比为1∶4∶4时,目标产物收率最大。该合成工艺简单、高效,适合放大生产。
Abstract:
The present work introduced one synthetic method for the medicine intermediate of anamorelin. 3-piperidine ethyl formate was firstly synthesized with 3-pipecolinic acid and ethanol as raw materials through esterification reaction. Then the addition reaction the 3-piperidine ethyl formate with di-tert-butyl pyrocarbonate was conducted under the alkaline condition. The 1-tert-butoxycarbonyl -3-benzyl -3-formic acid piperidine was obtained through hydrolysis with lithium hydroxide hydrate. Finally, the target product was purified via a resolution by employing R-(+)-α-methylbenzylamine as resolving agent. The compounds were characterized by 1H nuclear magnetic resonance spectroscopy and mass spectroscopy. The process optimization results found that the sodium carbonate demonstrated excellent catalytic performance for the reaction. The yield was highest with 1∶4∶4 mole ration of 1-tert-butyloxycarbonyl-3-benzyl-3-ethyl formate peridine/lithium hydroxide hydrate/ethanol and with sodium carbonate as alkali. The present synthetic method is suitable in industry application with its simple operation and high yield.

参考文献/References:

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备注/Memo

备注/Memo:

收稿日期:2017-02-24基金项目:国家自然科学基金(20471045)作者简介:陈楚珺,硕士研究生。E-mail:chujunchen0101@163.com*通讯作者:黄齐茂,博士,教授,博士研究生导师。E-mail:huangqim@163.com引文格式: 陈楚珺,冯瑾瑾,张勤,等. 阿拉莫林中间体的合成及表征[J]. 武汉工程大学学报,2018,40(3):243-249.
更新日期/Last Update: 2018-06-28