| 摘要 |
The present invention relates to a simplified method for synthesizing a pharmaceutically acceptable acid addition salt of (1S, 2R)-milnacipran of the formula (I): comprising: (a) reaction of phenylacetonitrile and (R)-epichlorhydrin in the presence of a base containing an alkaline metal, followed by a basic treatment, and by an acid treatment to obtain a lactone; (b) reaction of said lactone with MNEt2, wherein M represents an alkaline metal, or with NHEt2 in the presence of a Lewis acid-amine complex, to obtain an amide-alcohol; (c) reaction of said amide-alcohol with thionyl chloride to obtain a chlorinated amide; (d) reaction of said chlorinated amide with a phthalimide salt to obtain a phthalimide derivative; (e) hydrolysis of the phthalimide group to obtain (1S, 2R)-milnacipran, and (f) salification of (1S, 2R)-milnacipran in a suitable solvent system in the presence of a pharmaceutically acceptable acid. |
