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

HRID 720388Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 720388
[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

Komponenten

5

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-5794940666354acd844ae4f6fe1c658e
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07135479B2

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