Methyl isobutyrate → 1,1-Dimethylethyl (2R,6S)-4-({4-[1,1-dimethyl-2-(methyloxy)-2-oxoethyl]phenyl}methyl)-2,6-dimethyl-1-piperazinecarboxylate

HRID 43354

反応式

HRID 43354 の反応式
[CH3:1][CH:2]([CH3:7])[C:3]([O:5][CH3:6])=[O:4].C1([N-]C2CCCCC2)CCCCC1.[Li+].Br[C:23]1[CH:28]=[CH:27][C:26]([CH2:29][N:30]2[CH2:35][C@H:34]([CH3:36])[N:33]([C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[C@H:32]([CH3:44])[CH2:31]2)=[CH:25][CH:24]=1>C1(C)C=CC=CC=1.[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[CH3:1][C:2]([C:23]1[CH:24]=[CH:25][C:26]([CH2:29][N:30]2[CH2:35][C@H:34]([CH3:36])[N:33]([C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])[C@H:32]([CH3:44])[CH2:31]2)=[CH:27][CH:28]=1)([CH3:7])[C:3]([O:5][CH3:6])=[O:4]

参加物

7

反応物 3

HCID 11039Methyl isobutyrateHCID 10932176Lithium dicyclohexylamideHCID 252240971,1-Dimethylethyl (2R,6S)-4-[(4-bromophenyl)methyl]-2,6-dimethyl-1-piperazinecarboxylate

生成物 1

HCID 252242061,1-Dimethylethyl (2R,6S)-4-({4-[1,1-dimethyl-2-(methyloxy)-2-oxoethyl]phenyl}methyl)-2,6-dimethyl-1-piperazinecarboxylate収率 65.5%

試薬・触媒・溶媒 3

HCID 83681Tris(1,1-dimethylethyl)phosphine触媒HCID 1542701,5-Diphenylpenta-1,4-dien-3-one;palladium触媒HCID 1140Toluene溶媒

実験手順

A solution of methyl 2-methylpropanoate (188 ul, 1.64 mmol) in toluene (3 ml) was added to lithium dicyclohexylamide (362 mg, 1.93 mmol) under glove bag conditions. The suspension was stirred for 10 mins then added to a mixture of D43 (570 mg, 1.49 mmol) and bis(dibenzylideneacetone) palladium (0) (43 mg, 0.074 mmol). Tri(tert-butyl)phosphine (18 ul, 0.074 mmol) was added and the reaction mixture stirred at room temperature overnight. The solvent was removed in vacuo and chromatography eluting with 0-90% EtOAc/petroleum ether gave the title compound as a yellow oil (395 mg). δH (CDCl3, 250 MHz) 7.29 (4H, m), 4.07 (2H, m), 3.66 (3H, s), 3.46 (2H, s), 2.61 (2H, m), 2.12 (2H, dd), 1.58 (6H, s), 1.46 (9H, s), 1.29 (6H, d). MS (ES): MH+ 405.

後処理

  1. stirringthe reaction mixture stirred at room temperature overnight
  2. customThe solvent was removed in vacuo and chromatography
  3. washeluting with 0-90% EtOAc/petroleum ether

出典と根拠

ORDレコード
ord-c5561e98662a4bdd91f7af42e78611f5
出典データセット
uspto-grants-2013_09
特許番号
US08536182B2

関連ノート

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