Method for synthesis of (1S, 2R)-milnacipran
US8604241B2 · kind B2 · utility
Assignee
Inventors
Key dates
| Filing date | Jan 29, 2010 |
| Grant date | Dec 10, 2013 |
| Priority date | — |
| Expiry date | Sep 3, 2030 |
Classification
- Technology area (CPC C)Chemistry; Metallurgy
- CPC primaryC07C233/58
- WIPO fieldOrganic fine chemistry
- WIPO sectorChemistry
Abstract
The present invention relates to a method for synthesizing a pharmaceutically acceptable acid addition salt of (1S, 2R)-milnacipran comprising the following successive steps: (a) reaction of phenylacetonitrile and of (R)-epichlorhydrin in the presence of a base containing an alkaline metal, followed by a basic treatment, and then by an acid treatment in order 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, in order to obtain an amide-alcohol; (c) reaction of said amide-alcohol with thionyl chloride in order to obtain a chlorinated amide; (d) reaction of said chlorinated amide with a phthalimide salt in order to obtain a phthalimide derivative; (e) hydrolysis of the phthalimide group of said phthalimide derivative in order 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.
Source: USPTO / EPO open patent data. Objective bibliographic and citation counts.