摘要
改进了阿地溴铵中间体标题化合物的合成工艺。以苯酚和3-溴-1-丙醇为起始原料,经亲核取代、酯化、溴代3步反应得到标题化合物,其中3-苯氧基对甲苯磺酸丙酯不经柱层析直接利用乙酸乙酯和石油醚重结晶得到纯品(HPLC>98%),工艺总产率73.1%,产品纯度>98%,产品结构经~1HNMR确证。改进后的工艺操作简单、成本低廉、反应条件温和,适合工业化生产,为标题化合物的合成提供了一种新的、高效的制备方法。
The synthesis of title compound,a intermediate of aclidinium bromide was improved.The title compound was synthesized by three steps reaction of nucleophilic substitution,esterification,bromination from phenol and 3-bromo-1-propanol.Then the purity of 3-phenoxypropyl-4-methylbenzene sulfonate(HPLC>98%)was recrystallized directly with petroleum ether and ethylacetate without purifying by column chromatography.Then,in overall yield of 73.1%and purity>98%.The structures of product was characterized by^1HNMR.The improved reaction condition was easy to operating,low cost,and easy to be scaled up in industrialization,providing a new and efficient method for synthesis of key intermediate of the title compound.
作者
张宁
张宗磊
郭亚芸
段崇刚
杨利
孔祥雨
ZHANG Ning;ZHANG Zong-lei;GUO Ya-yun;DUAN Chong-gang;YANG Li;KONG Xiang-yu(Key Lab for Chemical Drug Research of Shandong Province,Shandong Academy of Pharmaceutical Science,Jinan 250101,China;Shandong Academy of Grape,Jinan 250100,China)
出处
《化学试剂》
CAS
北大核心
2020年第6期731-734,共4页
Chemical Reagents
基金
山东省重大科技创新工程项目(2019JZZY010520)。
关键词
阿地溴铵
支气管痉挛
3-苯氧基溴丙烷
合成
工艺改进
aclidinium bromide
bronchospasm
3-phenoxypropyl bromide
synthesis
process improvement
