Benzyl Bromide → (R)-2-((S)-3-benzyl-2-oxooxazolidin-4-yl)-N-methoxy-N-methylpropanamide

HRID 57377Notes

Reaction equation

HRID 57377 reaction equation
[CH3:1][O:2][N:3]([CH3:14])[C:4](=[O:13])[C@@H:5]([C@H:7]1[CH2:11][O:10][C:9](=[O:12])[NH:8]1)[CH3:6].Br[CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[H-].[Na+]>C1COCC1>[CH2:16]([N:8]1[C@@H:7]([C@@H:5]([CH3:6])[C:4]([N:3]([O:2][CH3:1])[CH3:14])=[O:13])[CH2:11][O:10][C:9]1=[O:12])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 90416286(R)-N-methoxy-N-methyl-2-((S)-2-oxooxazolidin-4-yl)propanamide

Product 1

HCID 90414536(R)-2-((S)-3-benzyl-2-oxooxazolidin-4-yl)-N-methoxy-N-methylpropanamideYield 97.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of crude (R)—N-methoxy-N-methyl-2-((S)-2-oxooxazolidin-4-yl)propanamide (1.3 g, 6.43 mmol) and (bromomethyl)benzene (1.30 mL, 11.4 mmol) in THF (25 mL) was added slowly sodium hydride (60% wt.; 0.643 g) at 0° C. [Caution: gas development!]. The ice bath was removed and the mixture was stirred for ˜2 hr. The mixture were diluted carefully with water and ethyl acetate. The reaction was repeated on the same scale and the mixtures were combined. The aqueous layer was separated and extracted with ethyl acetate (1×). The combined organic layers were dried over sodium sulfate, filtered off and concentrated under reduced pressure. The residue was purified by column chromatography [SiO2, 80 g, EtOAc/heptane=5/95 to 75/25] to provide (R)-2-((S)-3-benzyl-2-oxooxazolidin-4-yl)-N-methoxy-N-methylpropanamide (1.83 g) as a slightly yellow oil, which contained also N-methoxy-N-methylisobutyramide. MS m/z 293.7 (M+H)+; Rt-0.64 min.

Workup

  1. customThe ice bath was removed
  2. additionThe mixture were diluted carefully with water and ethyl acetate
  3. customThe aqueous layer was separated
  4. extractionextracted with ethyl acetate (1×)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered off
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography [SiO2, 80 g, EtOAc/heptane=5/95 to 75/25]

Sources & evidence

ORD record
ord-12634371ec2340af8d5e754eef2f07de
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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