Sodium hydride → (S)-2,2-dimethyl-4-[2-(5-trifluoromethyl-pyridin-2-yloxy)-ethyl]-oxazolidine-3-carboxylic acid tert-butyl ester

HRID 1807937Notes

Reaction equation

HRID 1807937 reaction equation
[OH:1][CH2:2][CH2:3][C@H:4]1[CH2:8][O:7][C:6]([CH3:10])([CH3:9])[N:5]1[C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].[H-].[Na+].Cl[C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=1>C1COCC1.C(OCC)(=O)C>[C:14]([O:13][C:11]([N:5]1[C@@H:4]([CH2:3][CH2:2][O:1][C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=2)[CH2:8][O:7][C:6]1([CH3:10])[CH3:9])=[O:12])([CH3:17])([CH3:16])[CH3:15]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 923422-Chloro-5-(trifluoromethyl)pyridineHCID 10847957tert-butyl (4S)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate

Product 1

HCID 59173205(S)-2,2-dimethyl-4-[2-(5-trifluoromethyl-pyridin-2-yloxy)-ethyl]-oxazolidine-3-carboxylic acid tert-butyl esterYield 82.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of tert-butyl (S)-4-(2-hydroxyethyl)-2,2-dimethyl-oxazolidine-3-carboxylate (300 mg; CAS 147959-18-0) in THF (4 ml) under an argon atmosphere was added sodium hydride (59 mg, 60% dispersion in oil). The resulting suspension was heated at 50° C. for 20 min and then cooled to 0° C. A solution of 2-chloro-5-trifluoromethyl-pyridine (222 mg) in THF (2 ml) was then added dropwise and the resulting mixture was heated at 70° C. for 3 h. The reaction mixture was cooled to room temperature and diluted with ethyl acetate. The mixture was washed with saturated brine, the phases were separated and the organic phase was dried over sodium sulphate and concentrated in vacuo. The residue was purified by column chromatography (SiO2; gradient: heptane/EtOAc) to give (S)-2,2-dimethyl-4-[2-(5-trifluoromethyl-pyridin-2-yloxy)-ethyl]-oxazolidine-3-carboxylic acid tert-butyl ester (393 mg, 82%) as a colourless oil. MS (ISP): 391.3 ([M+H]+).

Workup

  1. temperaturecooled to 0° C
  2. temperaturethe resulting mixture was heated at 70° C. for 3 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. washThe mixture was washed with saturated brine
  5. customthe phases were separated
  6. dry with materialthe organic phase was dried over sodium sulphate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by column chromatography (SiO2; gradient: heptane/EtOAc)

Sources & evidence

ORD record
ord-22efb5d81943433d94126144702e6e68
Source dataset
uspto-grants-2013_01
Patent number
US08357712B2

Reaction notes

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