托莫西汀合成工艺改进

Process improvement on the synthesis of atomoxetine

托莫西汀是一种高度选择性去甲肾上腺素再摄取抑制剂。本文在文献方法的基础上,对托莫西汀的合成工艺进行了改进。以3-氯-1-苯基丙-1-酮为原料,经不对称还原、Mitsunobu反应、缩合反应3步得到光学纯的目标产物,总收率26%。本研究将第3步甲胺化的封管操作改为了常压下反应,增大了工业化可行性。改进后的工艺操作简化,反应条件温和,为托莫西汀的制备提供了一种新的方法。

Atomoxetine is a highly selective norepinephrine reuptake inhibitor.Based on the analysis of the literature methods,the synthesis process of atomoxetine was improved.Using 3-chloropropiophenone-1 as the raw material,optically pure target product was obtained by asymmetric reduction,Mitsunobu reaction and condensation reaction in three steps,with a total yield of 26%.The third-step methylation sealing operation was changed to the reaction under normal pressure,which increased the feasibility of industrialization.The improved process operation was simplified and the reaction conditions were mild,which would provide a new method for the preparation of atomoxetine.