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 604680Notes

Reaction equation

HRID 604680 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]Br)=[N:27][C:28]([S:31][CH3:32])=[N:29][CH:30]=1>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

5

Reactant 3

HCID 24758Sodium hydrideHCID 150630115-Bromo-4-(bromomethyl)-2-(methylthio)pyrimidineHCID 23583229(4S,5R)-5-(3,5-bis(trifluoromethyl)phenyl)-4-methyloxazolidin-2-one2×

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×

Procedure

(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 1, 326 mg, 1.041 mmol) was dissolved in THF (7 mL) and cooled in an ice bath. To this solution was added NaH (27.3 mg, 1.136 mmol) all at once. The resulting bubbling/foaming mixture was stirred in an ice bath for 1 h followed by addition of 5-bromo-4-(bromomethyl)-2-(methylthio)pyrimidine (Step C, 282 mg, 0.946 mmol) in THF (3 mL). The resulting yellow mixture was stirred in an ice bath and allowed to warm to ambient overnight. The reaction crude was then quenched by adding NH4Cl (aq., sat.). The resulting mixture was worked up with brine, dried (Na2SO4), filtered and evaporated to give a yellow oil. The oil was purified by flash chromatography (SiO2, Biotage 40M cartridge). The column was eluted with a EtOAc/hexanes gradient mixture (0% to 20%). Related fractions were pooled and evaporated into a colorless glass/gum as the titled compound. LCMS calc.=530.99; found=532.00.

Workup

  1. temperaturecooled in an ice bath
  2. customThe resulting bubbling/foaming mixture
  3. stirringThe resulting yellow mixture was stirred in an ice bath
  4. temperatureto warm to ambient overnight
  5. customThe reaction crude
  6. customwas then quenched
  7. additionby adding NH4Cl (aq., sat.)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated
  11. customto give a yellow oil
  12. customThe oil was purified by flash chromatography (SiO2, Biotage 40M cartridge)
  13. washThe column was eluted with a EtOAc/hexanes gradient mixture (0% to 20%)
  14. customevaporated into a colorless glass/gum as the titled compound

Sources & evidence

ORD record
ord-6685f27cd8b147fba9578427cc3ff10e
Source dataset
uspto-grants-2011_03
Patent number
US07910592B2

Reaction notes

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