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

HRID 253081Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 253081
[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]

Komponenten

5

Edukt 3

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

Produkt 1

HCID 58248364(-)-(3S,4R)-3-(3,5-Bis-trifluoromethyl-benzyloxymethyl)-4-(4-fluoro-phenyl)-piperidine-1-carboxylic acid tert-butyl esterAusbeute 124,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-ccdb2fd9992d4b15b0aad8c1b628ded9
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07872022B2

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