U69593关键中间体1-氧杂螺[4.5]癸-7-烯的合成
A novel synthetic method of the key intermediate 1-oxaspiro[4.5]dec-7-ene of U69593
郑卫 1胡涛2
作者信息
- 1. 中国海洋大学医药学院,山东青岛 266003
- 2. 中国海洋大学医药学院,山东青岛 266003;扬子江药业集团有限公司,江苏泰州 225321
- 折叠
摘要
目的 对制备U69593的关键中间体1-氧杂螺[4.5]癸-7-烯(1)的合成方法进行改进.方法 以1,4-丁二醇为原料,经单羟基保护、氧化、酰胺化、烯烃复分解等8步反应合成中间体1.结果与结论 本研究首次报道了通过烯烃复分解反应构建环内碳碳双键合成中间体1的一种新方法,中间体1的结构经MS和NMR谱确证.该合成方法收率高,每步收率高于85％,总收率为45.2％.该方法重现性好,原料廉价易得,反应条件温和,操作简便安全,具有很好的放大合成基础和应用价值.
Abstract
U69593 is a common-used selective κ opioid receptor agonist.Herein,a novel synthetic route to the key intermediate 1-oxaspiro[4.5]dec-7-ene(1)of U69593 was reported.With 1,4-butanediol as the starting material,intermediate 1 was synthesized through eight steps of reactions,including mono-hydroxy protection,oxidation,amidation and olefin metathesis,with an overall yield up to 45.2％.The structure of intermediate 1 was confirmed by MS and NMR spectra.This method has the advantages of good reproducibility,low cost and easy availability of raw materials,mild reaction conditions,simple and safe operation,convenient scale-up synthesis and high application value.Furthermore,this is the first report on the synthesis of intermediate 1 via olefin metathesis reaction.
关键词
U69593/1-氧杂螺[4.5]癸-7-烯/氧杂螺环/烯烃复分解Key words
U69593/1-oxaspiro[4.5]dec-7-ene/oxaspirocycle/olefin metathesis reaction引用本文复制引用
出版年
2024
NETL
NSTL
万方数据