Triethyl phosphite → Donepezil

HRID 1645377ノート

反応式

HRID 1645377 の反応式
Br[CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][C:6]([O:13][CH3:14])=[C:7]([O:11][CH3:12])[CH:8]=2)[C:3]1=[O:15].P(OCC)(OCC)OCC.[CH2:26]([N:33]1[CH2:38][CH2:37][CH:36]([CH:39]=O)[CH2:35][CH2:34]1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C([N-]C(C)C)(C)C.[Li+]>[Pd].O1CCCC1>[CH3:12][O:11][C:7]1[CH:8]=[C:9]2[CH2:10][CH:2]([CH2:39][CH:36]3[CH2:35][CH2:34][N:33]([CH2:26][C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)[CH2:38][CH2:37]3)[C:3](=[O:15])[C:4]2=[CH:5][C:6]=1[O:13][CH3:14]

参加物

7

反応物 4

HCID 31215Triethyl phosphiteHCID 895841-Benzylpiperidine-4-carbaldehydeHCID 2724682Lithium diisopropylamideHCID 109236312-Bromo-5,6-dimethoxy-indan-1-one

生成物 1

HCID 3152Donepezil収率 50.8%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 8028Tetrahydrofuran溶媒

実験手順

There are many processes as disclosed in the prior arts for producing donepezil of formula 1. U.S. Pat. No. 4,895,841 wherein substituted 1-indanone-2-phosphonate prepared from 2-bromo-5,6-dimethoxyindanone and triethyl phosphite, is treated with 1-benzylpiperidine-4-carboxaldehyde in the presence of a strong base, such as lithium diisopropylamide (LDA), followed by catalytic reduction using palladium on carbon in tetrahydrofuran (40 volumes) to yield donepezil with an overall yield of 50.8%. This process however suffers with few limitations i.e. it employs triphenylphosphonium methoxymethyl chloride, which is expensive and toxic and the overall yield of this process is quite low. (scheme 1).

出典と根拠

ORDレコード
ord-a91868260619440cb738a37d927b78f0
出典データセット
uspto-grants-2012_02
特許番号
US08124783B2

反応ノート

読み込み中…