Sodium hydride → (R)-3-(2-chloropyrimidin-4-yl)-4-phenyloxazolidin-2-one

HRID 1850107Notes

Reaction equation

HRID 1850107 reaction equation
[C:1]1([C@@H:7]2[CH2:11][O:10][C:9](=[O:12])[NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:13][C:14]1[N:19]=[C:18](Cl)[CH:17]=[CH:16][N:15]=1.[H-].[Na+]>CN(C=O)C.CCOC(C)=O>[Cl:13][C:14]1[N:19]=[C:18]([N:8]2[C@H:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:11][O:10][C:9]2=[O:12])[CH:17]=[CH:16][N:15]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 775312,4-DichloropyrimidineHCID 730425(4R)-4-phenyl-1,3-oxazolidin-2-one

Product 1

HCID 86730136(R)-3-(2-chloropyrimidin-4-yl)-4-phenyloxazolidin-2-oneYield 54.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (R)-4-phenyloxazolidin-2-one (2.9484 g, 18.07 mmol) and 2,4-dichloropyrimidine (3.1872 g, 21.39 mmol, 1.184 equiv) in DMF (30 mL) was treated with NaH (95%, 0.4773 g, 18.89 mmol, 1.046 equiv), then the resulting mixture (yellow to red cloudy) was stirred at room temperature for 3 h. The reaction mixture was diluted with EtOAc (200 mL), washed with sat. NH4Cl (75 mL) and 4% aqueous NaCl (2×100 mL), dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 0 to 40%) provided (R)-3-(2-chloropyrimidin-4-yl)-4-phenyloxazolidin-2-one (2.7020 g, white sticky solid) in 46.9% yield. 1H NMR (400 MHz, CD3OD) δ 8.47 (d, J=5.6 Hz, 1H), 8.18 (d, J=6.1 Hz, 1H), 7.38-7.30 (m, 5H), 5.81 (dd, J=8.6, 3.5 Hz, 1H), 4.88 (t, J=8.6 Hz, 1H), 4.37 (dd, J=8.6, 3.5 Hz, 1H); MS m/z 276.4 (M+H)+.

Workup

  1. washwashed with sat. NH4Cl (75 mL) and 4% aqueous NaCl (2×100 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-26da954d0c5e449cb3da9bd743bbd496
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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