Preparation of paroxetine involving novel intermediates
AssigneeTeva Pharmaceutical Industries Ltd.
InventorsGideon Pilarski, Ilya Avrutov
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Abstract
Disclosed are processes for preparing novel carbamate intermediates of paroxetine comprising dealkylating N-alkylparoxetine by reaction thereof with a haloalkyl ester of a haloformic acid, in a suitable organic solvent. Also disclosed are processes for preparing paroxetine comprising hydrolyzing the novel carbamate intermediates in a suitable solvent. Paroxetine prepared by the above processes can be neutralized with hydrogen chloride and crystallized as paroxetine hydrochloride anhydrous, hemihydrate or as a solvate of isopropanol. The invention is further directed to the novel carbamate intermediates formed by the disclosed processes.
Claims67
A compound of formula (VII):
- 9
- wherein R1 is a haloalkyl other than 1-monohaloalkyl or perfluoroalkyl.
A process for preparing a compound of formula (VII) comprising reacting a compound of formula (V) with a compound of formula (VI) in a suitable organic solvent,
- 10
- wherein Z is a halogen;
- R1 is a haloalkyl other than 1-monohaloalkyl or perfluoroalkyl, and
- R2 is a lower alkyl.
A compound of formula (VIII):
- 11
A process for preparing a compound of formula (VIII):
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- comprising hydrolyzing a compound of formula (VII) wherein R1 is a haloalkyl other than 1-monohaloalkyl or perfluoroalkyl
- 13
- in the presence of propylene glycol monomethyl ether.
A process for preparing paroxetine comprising the steps of:
- (a) reacting a compound of formula (V) with a compound of formula (VI) in a suitable organic solvent, to form a compound of formula (VII),
- 14
- wherein Z is a halogen;
- R1 is a haloalkyl other than 1-monohaloalkyl or perfluoroalkyl, and
- R2 is a lower alkyl;
- and
- (b) and hydrolyzing the compound of formula (VII) to obtain paroxetine.
A process for preparing paroxetine comprising hydrolyzing a compound of formula (VII):
- 15
- wherein R1 is a haloalkyl other than 1-monohaloalkyl or perfluoroalkyl.
Dependencies are inferred from the claim text.