(1R,2S)-2-(3,4-二氟苯基)环丙胺的制备方法

Preparation Method of( 1R,2S)-2-( 3,4-difluorophenyl)-cyclopropylamine

制备(1R,2S)-2-(3,4-二氟苯基)环丙胺,优化制备工艺。以3,4-二氟溴苯为起始原料,经傅-克酰基化、立体选择性还原、环合、环丙烷化、水解、脱溴、酰胺化、霍夫曼消除共8步反应制备(1R,2S)-2-(3,4-二氟苯基)环丙胺。改进后的制备工艺所用原料和试剂工业上易得,价格低廉,操作方便,各步中间体易于纯化与储存,立体选择性较高,污染相对较小,环保压力小,易于工业上放大生产。

The preparation and optimization of（ 1R,2S）-2-（ 3,4-difluorophenyl）-cyclopropylamine were studied.（ 1R,2S）-2-（ 3,4-difluorophenyl）-cyclopropylamine was prepared from 3,4-difluoro- bromobenzene via eight steps including Friedel- crafts acylation,stereoselective reduction,cyclization,cyclopropanation,hydrolysis,debromination,amidation and Hoffman elimination. Not only the raw materials and reagents used in the improved process can be found easily in industry,but also the expenses were much lower. It can be found much easier when operating the reaction and purifying and storing the intermediates of each step. The stereo selectivity was higher with fewer wastes,it was more environmentally friendly. The improved process is more suitable for scale-up of industrial production.