Process for the preparation of citalopram
AssigneePharmachem Technologies Limited
InventorsAslam A. Malik, Hasan Palandoken, Joy A. Stringer, DerShing Huang, Antonio Romero, Olivier Dapremont
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Abstract
The present invention provides, inter alia, a novel process for the preparation of Citalopram, a known antidepressant.
Claims91
A method for preparing a salt of the compound of Formula III having the following structure:
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- said method comprising:
- (a) contacting a compound of Formula I having the following structure:
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- with 4-fluorophenyl magnesium bromide to form an intermediate of Formula II having the following structure:
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- (b) contacting said intermediate of Formula II with dimethylaminopropyl magnesium chloride in an organic solvent to form a reaction mixture;
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- (c) quenching said reaction mixture with an acid to form a product mixture comprising said salt of the compound of Formula III.
A method for preparing a compound of Formula IV having the following structure:
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- said method comprising:
- (a) contacting a salt of the compound of Formula III having the following structure:
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- with about 2 to about 10 equivalents of phosphoric acid to form a reaction mixture;
- (b) adding an organic solvent to said reaction mixture;
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- (c) quenching said reaction mixture with base to form a product mixture comprising said compound of Formula IV.
A method for preparing a compound of Formula V having the following structure:
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- said method comprising:
- (a) contacting a compound of Formula IV having the following structure:
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- with a mixture of cuprous cyanide and sodium cyanide to form a reaction mixture;
- (b) heating said reaction mixture until the reaction is complete;
- and
- (c) quenching said reaction mixture to form a product mixture comprising said compound of Formula V.
A method for preparing a compound of Formula VI having the following structure:
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- said method comprising:
- (a) dissolving a compound of Formula V having the following structure:
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- in an organic solvent to form a reaction mixture;
- and
- (b) contacting said reaction mixture with HBr to form a product mixture comprising said compound of Formula VI.
A method for removing demethyl- and/or didemethyl-impurities from a mixture of Citalopram containing demethyl- and/or didemethyl impurities in a solvent, said method comprising:
- (a) contacting said mixture of Citalopram with a scavenger resin having a functional group that is reactive with a primary or secondary amine to form resin-bound demethyl- and/or didemethyl impurities, wherein said scavenger resin is insoluble in said solvent;
- and
- (b) filtering said resin-bound demethyl- and/or didemethyl-impurities, thereby removing said demethyl and/or didemethyl-impurities from said mixture of Citalopram.
Dependencies are inferred from the claim text.