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

HRID 57351

Reaction equation

HRID 57351 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].[Cl:14][C:15]1[N:20]=[C:19](Cl)[CH:18]=[C:17]([Cl:22])[N:16]=1.[H-].[Na+]>CN(C=O)C.CCOC(C)=O>[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[CH:18]=[C:17]([Cl:22])[N:16]=[C:15]([Cl:14])[N:20]=1)[CH3:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 773782,4,6-TrichloropyrimidineHCID 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 69%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (R)-4-((R)-1-tert-butoxyethyl)oxazolidin-2-one (0.830 g, 4.43 mmol) and 2,4,6-trichloropyrimidine (0.894 g, 4.88 mmol, 1.10 equiv) in DMF (15 mL) was treated with NaH (60%, 0.248 g, 6.21 mmol, 1.40 equiv), then the resulting mixture (yellow) was stirred at room temperature for 1 h. The reaction mixture was diluted with EtOAc (100 mL) and quenched with saturated aqueous NaCl (100 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×30 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 0 to 40%) provided (R)-4-((R)-1-tert-butoxyethyl)-3-(2,6-dichloropyrimidin-4-yl)oxazolidin-2-one (1.0 g, white solid) in 69% yield. 1H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 4.70-4.66 (m, 2H), 4.45-4.40 (m, 2H), 1.26 (s, 9H), 1.04 (d, J=6.6 Hz, 3H); MS m/z 334.0 (M+H)+; Rt-1.10 min.

Workup

  1. customquenched with saturated aqueous NaCl (100 mL)
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with ethyl acetate (2×30 mL)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f655756615744c7c967620eabfea899a
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Linked notes

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