化工进展 ›› 2016, Vol. 35 ›› Issue (S2): 291-294.DOI: 10.16085/j.issn.1000-6613.2016.s2.050

• 生物与医药化工 • 上一篇    下一篇

盐酸地匹福林合成工艺

陈建超, 王晶, 谢卫斌, 孙铁民   

  1. 沈阳药科大学制药工程学院, 教育部基于靶点的药物设计与研究重点实验室, 辽宁 沈阳 110016
  • 收稿日期:2016-09-26 出版日期:2016-12-31 发布日期:2016-12-22
  • 通讯作者: 孙铁民,教授,博士生导师,主要从事天然产物合成和半合成、手性药物合成以及抗病毒药物的合成研究。E-mail:suntiemin@126.com。
  • 作者简介:陈建超(1990-),男,硕士研究生。

Study on the synthesis of dipivefrin hydrochloride

CHEN Jianchao, WANG Jing, XIE Wei, SUN Tiemin   

  1. Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China
  • Received:2016-09-26 Online:2016-12-31 Published:2016-12-22

摘要: 对盐酸地匹福林合成工艺进行研究,并对其进行纯度检测和结构确证。以邻苯二酚为主要起始原料,与氯乙酰氯发生傅克酰化反应得到3,4-二羟基-2'-氯苯乙酮,经特戊酰氯酯化得到4-(2-氯乙酰基)-1,2-二特戊酸苯酯,与N-甲基苄胺亲核取代得到1-(3,4-二特戊酰氧苯基)-2-(N-苄基甲基氨基)-1-酮,再经羰基还原、氢化脱苄、重结晶制得盐酸地匹福林。改进后的路线总收率为43.4%,显著提高了原工艺收率(23.6%),HPLC纯度达到98.98%,并通过MS、IR、1H-NMR、13C-NMR进行了结构确证。

关键词: 肾上腺素受体激动剂, 盐酸地匹福林, 工艺改进

Abstract: Based on the synthetic method of dipivefrin hydrochloride reported in literatures,the existing process was selected and optimized.In this work,the optimized method is a six-step synthetic route,including Friedel-Crafts reaction,esterification,N-alkylation,reduction of carbonyl,hydrogenation and recrystallization with the cheap and commercial available catechol as the starting material.The total yield of the optimized route is 43.4%,significantly improving the yield of the original process(23.6%),and the purity of the final product dipivefrin hydrochloride is 98.98%.Therefore,the optimized reaction method is in accordance with the requirements of industrial production.The structures of the target compound were confirmed by MS,IR,1H-NMR,and 13C-NMR.

Key words: adrenoceptor agonists, dipivefrin hydrochloride, process improvement

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