Process for the production of paroxetine
AssigneeRecordati S.A., Chemical and Pharmaceutical Company
InventorsRenzo Rossi, Stefano Turchetta, Maria Donnarumma
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Abstract
A process for the production of paroxetine is described, wherein N-substituted derivatives of 4-(p-fluorophenyl)-3-hydroxymethyl-1,2,3,6-tetrahydropyridine are treated according to the following sequence of reactions: (a) hydrogenation catalyzed by transition metal complexes with chiral diphosphinic ligands; (b) —OH derivatisation and nucleophilic substitution, the substituent being sesamol; (c) N-dealkylation. The process is highly stereospecific and brings about the formation of intermediates enriched with the desired isomeric components, which are converted into paroxetine in quantitative yields.
Claims14
Process for the synthesis of paroxetine, comprising the following steps:
- a) hydrogenation of a compound of formula (II), where R is a group selected from (C1-C5)alkyl, (C1-C5)carboxyalkyl, an optionally substituted phenyl, an optionally substituted benzyl, said hydrogenation being catalysed by a complex of a transition metal with chiral diphosphinic ligands, resulting in a 4R-enantiomerically enriched compound of formula (III):
- b) reaction of the compound of formula (III) with a reagent capable of transforming the —OH group into a leaving group, followed by nucleophilic substitution with sesamol (3,4-methylenedioxyphenol), resulting in a 4R-enantiomerically enriched derivative of formula (IV):
- c) N-dealkylation of compound (IV), resulting in paroxetine (I):
Dependencies are inferred from the claim text.