The trans-isomer(2)of milnacipran hydrochloride(1)was synthesized from(±)-(1S,2S)-2-hydroxymethyl-1-phenylcyclopropanecarboxylic acid via bromination, acyl chloridation, amidation, Gabriel reaction and HClsalt formation in 19% overall yield.
(±)-(1S,2S)-2-羟甲基-1-苯基环丙羧酸经溴化、酰氯化、酰胺化、Gabriel反应,最后成盐制得盐酸米那普仑(1)的反式异构体(2),总收率19%。