Sodium hydride → (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2,5-difluoropyrimidin-4-yl)oxazolidin-2-one

HRID 57482

Reaction equation

HRID 57482 reaction equation
[C:1]([O:5][C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[CH3:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[F:16][C:17]1[N:22]=[C:21](F)[C:20]([F:24])=[CH:19][N:18]=1.CCOC(C)=O.CCCCCCC>CN(C=O)C>[C:1]([O:5][C@@H:6]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:19]1[C:20]([F:24])=[CH:21][N:22]=[C:17]([F:16])[N:18]=1)[CH3:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 127973072,4,5-TrifluoropyrimidineHCID 21899848Ethylacetate heptaneHCID 90414930(R)-4-((R)-1-(tert-butoxy)ethyl)oxazolidin-2-one

Product 1

HCID 90414354(R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2,5-difluoropyrimidin-4-yl)oxazolidin-2-oneYield 68.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-4-((R)-1-(tert-butoxy)ethyl)oxazolidin-2-one (6.35 g, 33.9 mmol) in DMF (170 mL) under a nitrogen atmosphere at 0° C. was added sodium hydride (2.14 g, 50.9 mmol, 60%) portion wise over 3 minutes. The reaction mixture was then stirred for 2 hr at 0° C. whereupon 2,4,5-Trifluoropyrimidine (5 g, 37.3 mmol) was added and the reaction mixture allowed to stir 75 minutes at 0° C. then the mixture was allowed to warm to RT and stirred for 1 hr at RT. The reaction mixture was quenched with the slow addition of saturated solution of NH4Cl and the aqueous mixture extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 50%) provided a colorless oil of (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2,5-difluoropyrimidin-4-yl)oxazolidin-2-one (6.97 g, 23.1 mmol, 68% yield) which crystallizes upon standing. 1H NMR (400 MHz, CDCl3) 1.10 (d, J=6.26 Hz, 3H) 1.18 (s, 9H) 4.25-4.35 (m, 1H) 4.49-4.62 (m, 2H) 4.65-4.73 (m, 1H) 8.45 (d, J=1.57 Hz, 1H). LCMS m/z 246.1 (-t-butyl fragment) (M+H)+, Rt 0.91 min.

Workup

  1. additionwas added
  2. temperatureto warm to RT
  3. stirringstirred for 1 hr at RT
  4. customThe reaction mixture was quenched with the slow addition of saturated solution of NH4Cl
  5. extractionthe aqueous mixture extracted with EtOAc
  6. washwashed with water, brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-7be0f1a2abf947d0bca99fe273767ee8
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Linked notes

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