维兰特罗关键手性中间体的合成工艺改进

摘要

(5R)-5-(2,2-二甲基-4H-1,3-苯并二氧杂环己烯-6-基)-1,3-唑烷-2-酮(Ⅰ)是合成维兰特罗的关键手性中间体.以2-溴-1-(2,2-二甲基-4H-1,3-苯并二氧杂环己烯-6-基)乙酮(Ⅱ)为原料,通过还原、胺化和成环反应得到目标产物的消旋体Ⅷ,然后再用L-( +)-酒石酸拆分得到目标产物Ⅰ,ee值为90%.产物结构经1HNMR确认.%(5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one(Ⅰ) is a key chiral intermediate of vilanterol.Using 2-bromo-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-ethanone (Ⅱ) as a raw material,we obtained the racemateⅧby reduction,amination,and cyclization reactions.Then we obtained the target productⅠwith ee value of 90% after separating the racemateⅧby L-( +)-tartaric acid.Furthermore,we confirmed the structure of the product by 1 HNMR.