Sodium hydride → (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2,6-dichloropyrimidin-4-yl)oxazolidin-2-one

HRID 57342

Reaction equation

HRID 57342 reaction equation
[H-].[Na+].[Cl:3][C:4]1[N:9]=[C:8](Cl)[CH:7]=[C:6]([Cl:11])[N:5]=1.[C:12]([O:16][C@@H:17]([C@H:19]1[CH2:23][O:22][C:21](=[O:24])[NH:20]1)[CH3:18])([CH3:15])([CH3:14])[CH3:13].CCOC(C)=O.CCCCCCC>CN(C=O)C.CCOC(C)=O>[C:12]([O:16][C@@H:17]([C@H:19]1[CH2:23][O:22][C:21](=[O:24])[N:20]1[C:8]1[CH:7]=[C:6]([Cl:11])[N:5]=[C:4]([Cl:3])[N:9]=1)[CH3:18])([CH3:13])([CH3:14])[CH3:15]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 773782,4,6-TrichloropyrimidineHCID 21899848Ethylacetate heptaneHCID 90414930(R)-4-((R)-1-(tert-butoxy)ethyl)oxazolidin-2-one

Product 1

HCID 90414426(R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2,6-dichloropyrimidin-4-yl)oxazolidin-2-oneYield 65.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a round bottom flask was added NaH (0.54 g, 13.5 mmol, 57% dispersion in mineral oil) to a solution of 2,4,6-trichloropyrimidine (1.22 ml, 10.6 mmol) and (R)-4-((R)-1-(tert-butoxy)ethyl)oxazolidin-2-one (1.8 g, 9.61 mmol) in DMF (32 mL) at 0° C. (ice bath) under a bubbler. The yellow suspension was then stirred at 0° C. for 15 min and then the ice bath was removed and reaction mixture allowed to stir 1 hr at room temperature. Reaction mixture was diluted with EtOAc and then carefully quenched with brine. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (EtOAc/Heptane 0 to 100%) provided (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2,6-dichloropyrimidin-4-yl)oxazolidin-2-one (2.1 g, 6.28 mmol, 65% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ 1.04 (d, J=6.55 Hz, 3H) 1.26 (s, 9H) 4.38-4.48 (m, 2H) 4.64-4.75 (m, 2H) 8.22 (s, 1H). LCMS m/z 334.1 (M+H)+, Rt 1.10 min.

Workup

  1. customthe ice bath was removed
  2. customreaction mixture
  3. stirringto stir 1 hr at room temperature
  4. customReaction mixture
  5. customcarefully quenched with brine
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with EtOAc
  8. dry with materialThe combined organic layers were dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-a7e31ec28616490589153cf7ac4b0516
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Linked notes

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