Sodium hydride → (R)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one

HRID 57359

Reaction equation

HRID 57359 reaction equation
[H-].[Na+].[Si:3]([O:20][CH2:21][C@H:22]1[CH2:26][O:25][C:24](=[O:27])[NH:23]1)([C:16]([CH3:19])([CH3:18])[CH3:17])([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:28][C:29]1[N:34]=[C:33](F)[CH:32]=[CH:31][N:30]=1>CN(C=O)C>[Si:3]([O:20][CH2:21][C@H:22]1[CH2:26][O:25][C:24](=[O:27])[N:23]1[C:31]1[CH:32]=[CH:33][N:34]=[C:29]([F:28])[N:30]=1)([C:16]([CH3:17])([CH3:18])[CH3:19])([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1377162,4-DifluoropyrimidineHCID 89766177HCID 89766177, compound

Product 1

HCID 90416256(R)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-oneYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (34 mg, 0.84 mmol, 1.5 equiv) was carefully added to a solution of (R)-4-(((tert-butyldiphenylsilyl)oxy)methyl)oxazolidin-2-one (200 mg, 0.563 mmol) in DMF (2.8 mL). The mixture was stirred at room temperature for 20 minutes and then 2,4-difluoropyrimidine (0.072 mL, 0.84 mmol, 1.5 equiv) was added (bubbling). The yellow suspension was stirred for minutes and the reaction was then carefully quenched with saturated aqueous ammonium chloride (5 mL). Water (20 mL) was added and the mixture was extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (20 mL), dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane 30%) provided (R)-4-(((tert-butyldiphenylsilyl)oxy)methyl)-3-(2-fluoropyrimidin-4-yl)oxazolidin-2-one (0.185 g, sticky colorless oil) in 73% yield. 1H NMR (400 MHz, CDCl3) δ 8.44 (dd, J=5.8, 2.2 Hz, 1H), 8.12 (dd, J=5.8, 3.4 Hz, 1H), 7.58 (m, 2H), 7.48-7.32 (m, 6H), 7.23 (m, 2H), 4.80 (m, 1H), 4.65 (dd, J=8.6, 3.0 Hz, 1H), 4.55 (m, 1H), 4.18 (dd, J=11.1, 3.5 Hz, 1H), 3.83 (dd, J=11.1, 2.1 Hz, 1H), 1.04 (s, 9H). MS m/z 452.3 (M+H)+; Rt-1.15 min.

Workup

  1. custom(bubbling)
  2. stirringThe yellow suspension was stirred for minutes
  3. customthe reaction was then carefully quenched with saturated aqueous ammonium chloride (5 mL)
  4. additionWater (20 mL) was added
  5. extractionthe mixture was extracted with ethyl acetate (2×25 mL)
  6. washThe combined organic extracts were washed with saturated aqueous sodium chloride (20 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-cf2809937dce4b0f8a4165f036dc6fe0
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Linked notes

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