5,6-Dimethoxy-1-indanone → Donepezil

HRID 1069421Notes

Reaction equation

[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C:8](=[O:14])[CH2:7][CH2:6]2.[CH2:15]([N:22]1[CH2:27][CH2:26][CH:25]([CH:28]=O)[CH2:24][CH2:23]1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C([N-]C(C)C)(C)C.[Li+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[CH2:6][CH:7]([CH2:28][CH:25]3[CH2:24][CH2:23][N:22]([CH2:15][C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[CH2:27][CH2:26]3)[C:8](=[O:14])[C:9]2=[CH:10][C:11]=1[O:12][CH3:13]

Participants

Reactant 3

HCID 750185,6-Dimethoxy-1-indanone

HCID 895841-Benzylpiperidine-4-carbaldehyde

HCID 2724682Lithium diisopropylamide

Product 1

HCID 3152Donepezil

Procedure

As it was disclosed in Example 3 and 4 of JP-A 64-79151(1989), indanone derivative was produced by reacting 5,6-dimethoxy-1-indanone with 1-benzyl-4-formylpiperidine in the presence of strong base such as lithium diisopropylamide (Example 3), followed by reduction (Example 4) for example. According to this method, yield for Donepezil through Example 3 and 4 was 50.8% (62%×82%).

Sources & evidence

ORD record: ord-b08503b745ae44b6b3adc8bc1144e125
Source dataset: uspto-grants-2001_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06252081B1

Reaction notes

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