Process for the preparation of donepezil hydrochloride
AssigneeAurobindo Pharma Ltd
InventorsMahesh Nagarimadugu, Arun Gupta, Ramesh Dandala, Sivakumaran Meenakshisunderam
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Abstract
The present invention relates to an improved process for the preparation of 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride of Formula I.
Claims20
An improved process for the preparation of 1-benzyl4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride of Formula I.
- which comprises,
- (i) reacting 5,6-dimethoxy-1-indanone (II),
- with 1-benzyl-4-piperidinecarboxaldehyde (III),
- in presence of base and an antioxidant in a solvent to produce 1-benzyl-4-[5,6-dimethoxy-1-indanon)-2-ylidenyl]methyl]piperidine solvate (IV),
- wherein solvate is derived from hydrocarbon such as toluene,
- (ii) hydrogenating the compound (IV) with metal catalyst in a solvent or mixture of solvents to produce 1-benzyl4-[(5,6-dimethoxy-1-indanon)-2-yl] methylpiperidine hydrochloride of Formula I,
- (iii)optionally treating aqueous solution of 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride (I) containing 4-[5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine (VI) ≧0.4% by HPLC,
- with benzyl halide in presence of base and phase transfer catalyst in a solvent to produce 1-benzyl4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride (I).
A process to prepare 1-Benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride of Formula I
- substantially free of compound of Formula V
- comprising,
- (i) reacting 5,6-dimethoxy-1-indanone (II),
- with 1-benzyl-4-piperidinecarboxaldehyde (III),
- in presence of base and an antioxidant in a solvent to produce 1-benzyl-4-[5,6-dimethoxy-1-indanon)-2-ylidenyl]methyl]piperidine solvate (IV),
- wherein solvate is derived from hydrocarbon such as toluene,
- (ii) hydrogenating the compound (IV) with metal catalyst in a solvent or mixture of solvents to produce 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methylpiperidine hydrochloride of Formula I.
A process for the preparation of pure 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-2-yl]methylpiperidine hydrochloride of Formula I
- which comprises
- i) treating aqueous solution of 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride (I) containing 4-[5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine (VI) >0.4% by HPLC,
- with benzyl halide in presence of base and phase transfer catalyst in a solvent to produce 1-benzyl-4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride (I).
1-Benzyl4-[(5,6-dimethoxy-1-indanon)-2-yl]methylpiperidine hydrochloride of Formula I
- substantially free of compound of Formula V.
Dependencies are inferred from the claim text.