Sodium hydride → 4-(6-Fluoro-indol-1-ylmethyl)-piperidine-1-carboxylic acid benzyl ester

HRID 28483ノート

反応式

HRID 28483 の反応式
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.[H-].[Na+].S(O[CH2:24][CH:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)=[O:32])[CH2:27][CH2:26]1)(C1C=CC(C)=CC=1)(=O)=O>CN(C)C=O>[CH2:34]([O:33][C:31]([N:28]1[CH2:29][CH2:30][CH:25]([CH2:24][N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:10]=3)[CH:6]=[CH:7]2)[CH2:26][CH2:27]1)=[O:32])[C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1

参加物

5

反応物 3

HCID 24758Sodium hydrideHCID 3512786-FluoroindoleHCID 218920784-(Toluene-4-sulfonyloxymethyl)-piperidine-1-carboxylic acid benzyl ester

生成物 1

HCID 692065134-(6-Fluoro-indol-1-ylmethyl)-piperidine-1-carboxylic acid benzyl ester収率 101%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

To 6-fluoroindole (1.35 g, 10.0 mmol) in N,N-dimethylformamide (100 mL) was added a 60% mineral oil dispersion of sodium hydride (0.44 g, 11 mmol). The mixture was stirred at room temperature under nitrogen for 30 min, then 4-tosyloxymethyl-N-carbobenzyloxypiperidine (4.0 g, 10 mmol) added and the mixture heated at 70° C. under nitrogen for 16 hours. The solvent was removed in vacuum and replaced with methylene chloride (350 mL). The solution was washed with 250 mL portions of 2N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and saturated brine and dried over sodium sulfate. Filtration, concentration in vacuum and column chromatography on silica gel with methylene chloride as eluent gave 3.7 g of 4-(6-fluoro-indol-1-ylmethyl)-piperidine-1-carboxylic acid benzyl ester. This material was dissolved in ethyl acetate (100 mL), 10% Pd on carbon (0.50 g) and cyclohexene (3.2 g, 40 mmol) added, and the mixture refluxed under nitrogen for 2 hours. Filtration through celite, followed by concentration in vacuum gave 2.1 g of the title compound as a white solid. 1H-NMR (CDCl3) doublet of doublets 7.5 δ (1 H); doublet 7.0 δ (1 H); doublet of doublets 6.95 δ (1 H); triplet of doublets 6.82 δ (1 H); doublet 6.42 δ (1 H); doublet 3.9 δ (2 H); doublet 3.02 δ (1 H); triplet 2.5 δ (2 H); doublet 1.5 δ (2 H); multiplet 1.2 δ (2 H).

後処理

  1. temperaturethe mixture heated at 70° C. under nitrogen for 16 hours
  2. customThe solvent was removed in vacuum
  3. washThe solution was washed with 250 mL portions of 2N aqueous hydrochloric acid, saturated aqueous sodium bicarbonate and saturated brine
  4. dry with materialdried over sodium sulfate
  5. filtrationFiltration, concentration in vacuum and column chromatography on silica gel with methylene chloride as eluent

出典と根拠

ORDレコード
ord-b0c1e59602784fd09205cd1fc328739d
出典データセット
uspto-grants-2008_09
特許番号
US07419986B2

反応ノート

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