Sodium hydride → HCID 67500771, compound

HRID 1187777Notes

Reaction equation

HRID 1187777 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=2)[CH2:11][O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[Br:26][C:27]1[CH:28]=[CH:29][C:30]([CH:33](OS(C(F)(F)F)(=O)=O)[C:34]([F:37])([F:36])[F:35])=[N:31][CH:32]=1>C1COCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@@H:12]([CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([NH:21][CH:33]([C:30]3[CH:29]=[CH:28][C:27]([Br:26])=[CH:32][N:31]=3)[C:34]([F:37])([F:36])[F:35])=[CH:19][CH:20]=2)[CH2:11][O:10][C:9]1([CH3:23])[CH3:22])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 66705807HCID 66705807, compoundHCID 86664596HCID 86664596, compound

Product 1

HCID 67500771HCID 67500771, compoundYield 38%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a stirred solution of (S)-4-[2-(4-amino-phenyl)-ethyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (150 mg, example 6b) in dry THF (0.2 ml) under an argon atmosphere was added sodium hydride (34 mg, 60% dispersion in mineral oil) and stirring was continued for 15 minutes. Trifluoro-methanesulfonic acid 1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethyl ester (182 mg) was then added and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate and washed sequentially with water and with saturated brine. The organic phase was separated, dried over sodium sulphate, and concentrated in vacuo. The reside was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give (S)-4-(2-{4-[1-(5-bromo-pyridin-2-yl)-2,2,2-trifluoro-ethylamino]-phenyl}-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (99 mg, 38%) as a yellow oil. MS (ISP): 560.1 ([{81Br}M+H]+), 558.1 ([{79Br}M+H]+).

Workup

  1. stirringthe mixture was stirred overnight at room temperature
  2. washwashed sequentially with water and with saturated brine
  3. customThe organic phase was separated
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated in vacuo
  6. customThe reside was purified by column chromatography (SiO2; gradient: heptane/EtOAc)

Sources & evidence

ORD record
ord-0cdd725814be4df2ae59751e88b1e89d
Source dataset
uspto-grants-2014_03
Patent number
US08673950B2

Reaction notes

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