一种新的马来酸氟伏沙明的合成方法

Flavoxamine maleate is an excellent antidepressive drug. In the literatures,it was synthesized by the use of 4-(trifluoromethyl)aniline or 4-(trifluoromethyl)benzonitrile as starting materials and 5- methoxy-4’-(trifluoromethylphenyl)valerophenone as a key intermediate. However,the methods in literatures have some disadvantages , such as the use of expensive materials, heavy pollution of environment , long reaction time and low yield of the product (only 30-40% overall yield). We report herein an environmentally friendly synthetic method of flavoxamine maleate, which used 4-(trifluoromethyl) benzoic acid and tetrahydrofuran as starting materials and FeCl3 as catalyst for the coupling of acid chloride with Grignard reagent. The flavoxamine maleate was synthesized in 46% overall yield, through the oximation, etheration and salification of the intermediate, successively.This method has some advantages, such as the use of commercially available materials, low cost, short production period , high yield and light pollution.