Sodium hydride → (-)-(3S,4R)-3-(3,5-Bis-trifluoromethyl-benzyloxymethyl)-4-(4-fluoro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 253081ノート

反応式

HRID 253081 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@H:10]([CH2:21][OH:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[F:25][C:26]([F:40])([F:39])[C:27]1[CH:28]=[C:29]([CH:32]=[C:33]([C:35]([F:38])([F:37])[F:36])[CH:34]=1)[CH2:30]Br>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@@H:11]([C:14]2[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=2)[C@H:10]([CH2:21][O:22][CH2:30][C:29]2[CH:32]=[C:33]([C:35]([F:37])([F:38])[F:36])[CH:34]=[C:27]([C:26]([F:25])([F:39])[F:40])[CH:28]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 10018204tert-Butyl (3S,4R)-4-(4-fluorophenyl)-3-(hydroxymethyl)piperidine-1-carboxylate

生成物 1

HCID 58248364(-)-(3S,4R)-3-(3,5-Bis-trifluoromethyl-benzyloxymethyl)-4-(4-fluoro-phenyl)-piperidine-1-carboxylic acid tert-butyl ester収率 124.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (3S,4R)-4-(4-fluoro-phenyl)-3-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (1.58 g, 5.11 mmol) in 30 ml DMF were added 0. 29 g (6.0 mmol) sodium hydride (50% in mineral oil) at 0° C. The reaction mixture was allowed to warm to room temperature. After 20 min. 3,5-bis(trifluoromethyl)benzyl bromide (3.14 g, 10.2 mmol) was added. Stirring at room temperature for 2 h was followed by quenching with water and extraction with three portions of tert-butyl methyl ether. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel, heptane/ethyl acetate) to give 3.4 g (>100%) of the title compound as a white solid.

後処理

  1. customat 0° C
  2. customby quenching with water and extraction with three portions of tert-butyl methyl ether
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by flash column chromatography (silica gel, heptane/ethyl acetate)

出典と根拠

ORDレコード
ord-ccdb2fd9992d4b15b0aad8c1b628ded9
出典データセット
uspto-grants-2011_01
特許番号
US07872022B2

反応ノート

読み込み中…