| abstract |
The invention relates to a synthesis method of (1S,2R)-milnacipran. Specifically relates to the method for synthesizing the pharmaceutically acceptable acid addition salt of (1S,2R)-milnacipran, it comprises following successive steps: (a) phenylacetonitrile and (R)-epichlorohydrin in the base containing alkali metal Reaction under the condition that exists, after base treatment, acid treatment, get lactone; (b) under the condition that Lewis acid-amine complex exists, this lactone and MNEt 2 (M represents alkali metal) or NHEt 2 reaction, Obtain amide alcohol; (c) react amide alcohol with thionyl chloride to obtain amide chloride; (d) react amide chloride with phthalimide salt to obtain phthalimide derivative (e) the phthalimide group of the phthalimide derivative is hydrolyzed to obtain (1S, 2R)-milnacipran; (f) in the presence of a pharmaceutically acceptable acid Under certain conditions, (1S,2R)-milnacipran is salted in a suitable solvent system. |