Patent ID: 7166729
Filing Date: 2007-01-23
Classification: A61P,C07C,C07D

Abstract:
1. A process for the preparation of citalopram which comprises: (a) treating 5-formylphthalide of formula with a hydroxylamine of formula wherein R represents a hydrogen atom or a substituent R′ inert under the conditions of a Grignard reaction selected from the group consisting of (C wherein R is as defined above; (b) reacting the oxime thus obtained with a 4-fluorophenylmagnesium halide; when R═R′ (IIIb) or after substitution of R by R′ when R═H (IIIa) to form an intermediate ketone of formula wherein R′ is as defined above and R″ represents MgHal (IVa) wherein Hal is halogen, or hydrogen (IVb); (c) reacting the intermediate ketone of formula IV with a [3-(dimethylamino)propyl]magnesium halide to form an intermediate diol of formula wherein R′ is as defined above; and (d) cyclizing the intermediate diol of formula V to form a substituted oxime of formula wherein R′ is as defined above; (e) optionally, when R is not H removing the group R′ of the substituted oxime of formula VI to form an unsubstituted oxyamino group of the oxime of formula (f) converting the unsubstituted oxyamino group of the oxime of formula VII into a nitrile group to give citalopram or one of its pharmaceutical acceptable salts; or (e′) optionally, when R′ is triphenylmethyl or diphenylmethyl, converting the substituted oxyamino group of the oxime of formula VI into nitrile by treatment with a mixed anhydride of formula wherein R′″ represents a C