METHOD FOR PREPARING PAROXETINE Russian patent published in 2004 - IPC

FIELD: organic chemistry, chemical technology, pharmacy.

SUBSTANCE: invention relates to a method for preparing paroxetine that involves the following steps: a) hydrogenation of compound of the formula (II)

wherein R means group taken among (C₁-C₅)-alkyl, (C₁-C₅)-carboxyalkyl, optionally substituted phenyl and optionally substituted benzyl and hydrogenation reaction is catalyzed with complex compound of transient metal with chiral diphosphine ligands wherein transient metal is taken among ruthenium, iridium and rhodium, and hydrogenation process is carried out under pressure from 1 to 150 atm, in alcoholic or halogenated solvent or their mixture at temperature from 60^oC to 150^oC that results to formation of compound of the formula (III):

enriched with 4R-enantiomer; b) reaction of compound of the formula (III) with reagent that is able to transform OH-group to removing group and taken among tosyl chloride, methanesulfonyl chloride, benzenesulfonyl chloride that is added to compound of the formula (III)

at temperature between -20^oC and +25^oC in the presence of inert solvent and basic compound followed by its nucleophilic substitution with sesamol-(3,4-methylenedioxyphenol), its addition as mixture with alcoholic solvent in the presence of a base and formed mixture is heated for 2-4 h to yield derivative of the formula (IV):

enriched with 4R-enantiomer; c) N-dealkylation of compound of the formula (IV) to yield paroxetine. Method elicits high stereospecificity and results to formation of intermediate compounds enriched with required isomeric components that are converted with quantitative yield.

EFFECT: improved preparing method.

8 cl, 8 dwg, 2 tbl, 9 ex