Donepezil Hydrochloride → 2-Pyridin-4-ylmethyl-indan-1-one

HRID 480396

Reaction equation

CO[C:3]1[CH:4]=[C:5]2[CH2:14][CH:13]([CH2:15][CH:16]3[CH2:21][CH2:20][N:19](CC4C=CC=CC=4)[CH2:18][CH2:17]3)[C:11](=[O:12])[C:6]2=[CH:7][C:8]=1OC.Cl.C1(=O)C2C(=CC=CC=2)CC1>>[N:19]1[CH:20]=[CH:21][C:16]([CH2:15][CH:13]2[CH2:14][C:5]3[C:6](=[CH:7][CH:8]=[CH:3][CH:4]=3)[C:11]2=[O:12])=[CH:17][CH:18]=1

Participants

Reactant 2

HCID 5741Donepezil Hydrochloride

HCID 67351-Indanone

Product 1

HCID 149398002-Pyridin-4-ylmethyl-indan-1-one

Procedure

U.S. Pat. No. 6,252,081 teaches the preparation of Donepezil HCl by the reaction of 1-indanone derivative with carbonate ester. The resulting 2-alkoxycarbonyl-1-indanone derivative is halogenated with (4-pyridyl)methyl or a salt thereof and decarboxylated successively to give 2-(4-pyridyl)methyl-1-indanone derivative. On reacting the 2-(4-pyridyl)methyl-1-indanone derivative with benzyl bromide, their quarternary ammonium salts are formed, which on reduction with platinum oxide catalyst gives Donepezil HCl (Examples 1 to 3). Overall yield of Donepezil HCl 82% (98%×85%×100%×99%).

Sources & evidence

ORD record: ord-ea93d46d6e9a41869731217743368257
Source dataset: uspto-grants-2003_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06649765B1

Linked notes

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