Sodium hydride → (4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-bromo-2-(methylthio)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

HRID 1508518Notes

Reaction equation

HRID 1508518 reaction equation
[F:1][C:2]([F:21])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[NH:15][C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[H-].[Na+].[Br:24][C:25]1[C:26]([CH2:33]S(C)(=O)=O)=[N:27][C:28]([S:31][CH3:32])=[N:29][CH:30]=1.[NH4+].[Cl-]>C1COCC1>[F:21][C:2]([F:1])([F:20])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:33][C:26]3[C:25]([Br:24])=[CH:30][N:29]=[C:28]([S:31][CH3:32])[N:27]=3)[C@H:14]2[CH3:19])[CH:6]=[C:7]([C:9]([F:10])([F:11])[F:12])[CH:8]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-oneHCID 772307075-Bromo-2-(methylsulfanyl)-4-[(methylsulfonyl)methyl]pyrimidine

Product 1

HCID 57576287(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-bromo-2-(methylthio)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (12.00 g, 38.3 mmol) in THF (200 mL) was cooled to 0° C. NaH (0.919 g, 38.3 mmol) was added. The mixture was stirred at 0° C. for 30 min. The title compound from Step A (10.0 g, 31.9 mmol) in THF (30 mL) was added. The mixture was stirred at 0° C. and then room temperature for 4 h. Saturated NH4Cl (10 mL) was added. The mixture was extracted with ethyl acetate (3×100 mL). The combined organic fractions were washed with brine (saturated, 20 mL), dried (Na2SO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel Biotage 65i, eluting with EtOAc/hexane (20/80) to give the title compound as a colorless solid. 1H NMR (CDCl3, 500 MHz) δ 8.57 (s, 1H), 7.94 (s, 1H), 7.82 (s, 2H), 5.86 (d, J=8.5 Hz, 1H), 4.97 (d, J=18.0 Hz, 1H), 4.46 (m, 1H), 4.28 (d, J=17.5 Hz, 1H), 2.60 (s, 3H), 0.83 (d, J=6.5 Hz, 3H).

Workup

  1. stirringThe mixture was stirred at 0° C.
  2. waitroom temperature for 4 h
  3. extractionThe mixture was extracted with ethyl acetate (3×100 mL)
  4. washThe combined organic fractions were washed with brine (saturated, 20 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel Biotage 65i
  9. washeluting with EtOAc/hexane (20/80)

Sources & evidence

ORD record
ord-ce7bbd8d40584a33a951f5689038432d
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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