Pierre Fabre Medicament

Commissariat &#xc0; L'&#xc9;nergie Atomique Et Aux &#xc9;nergies Alternatives

Warner-lambert Company

Marc Nicolas

Charles Mioskowski

Vanessa Gonnot

Rachid Baati

Eric Doris

Blandine Laboue

Laurent Subra

Dominique Depernet

Paul Hellier

Sébastien Leroux

Laurent Larquetoux

Catherine Diard

The present invention relates to the use of the vinyl quinuclidine enantiomer (R) of the following formula 2 as a synthesis intermediate in the preparation of (R)-mequitazine.

Vinyl quinuclidine useful as a synthesis intermediate in the preparation of (R)-mequitazine

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 MNEt, wherein M represents an alkaline metal, or with NHEtin 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.

Method for synthesis of (1S, 2R)-milnacipran

The invention relates to a 1-aza-bicyclo[2.2.2]oct-2-en-3-ylmethyl acetate of the formula (I), wherein said compound is useful as a synthesis intermediate for the production of mequitazine.

Quinuclidine derivative useful in the preparation of mequitazine

Process for the preparation of

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Gaillac, France

Marc Nicolas