Sodium hydride → (4R,5R)-3-[3,5-Bis(trifluoromethyl)benzyl]-5-[2-iodo-5-(trifluoromethyl)phenyl)-4-methyl-1,3-oxazolidin-2-one

HRID 607087Notes

Reaction equation

HRID 607087 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[C@H:12]1[O:16][C:15](=[O:17])[NH:14][C@@H:13]1[CH3:18].[H-].[Na+].Br[CH2:22][C:23]1[CH:28]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:26]=[C:25]([C:33]([F:36])([F:35])[F:34])[CH:24]=1>C1COCC1>[F:30][C:29]([F:31])([F:32])[C:27]1[CH:28]=[C:23]([CH:24]=[C:25]([C:33]([F:36])([F:34])[F:35])[CH:26]=1)[CH2:22][N:14]1[C@H:13]([CH3:18])[C@@H:12]([C:3]2[CH:4]=[C:5]([C:8]([F:9])([F:10])[F:11])[CH:6]=[CH:7][C:2]=2[I:1])[O:16][C:15]1=[O:17]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 59726151(4R,5R)-5-[2-iodo-5-(trifluoromethyl)phenyl]4-methyl-1,3-oxazolidin-2-one2×

Product 1

HCID 59135170(4R,5R)-3-[3,5-Bis(trifluoromethyl)benzyl]-5-[2-iodo-5-(trifluoromethyl)phenyl)-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(4R,5R)-5-[2-iodo-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 12, 1.451 g, 3.910 mmol) was dissolved in anhydrous THF (30 mL) and cooled in an ice bath. Sodium hydride (60% w/w in mineral oil, 172 mg, 4.301 mmol) was added into the reaction mixture all in once. The reaction was stirred cold (ice bath) for 30 min followed by addition of 1-(bromomethyl)-3,5-bis(trifluoromethyl)benzene (1.078 mL, 1.80 mg, 5.865 mmol). The crude mixture was cooled (ice bath) and quenched adding by NH4Cl (aq, sat.) when reaction time was 5 hours. Reaction crude was extracted with ethyl acetate. The combined organic extracts were dried over Na2SO4, filtered, and concentrated to an oil. The oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge, EtOAc/hexanes) to afford (4R,5R)-3-[3,5-bis(trifluoromethyl)benzyl]-5-[2-iodo-5-(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one. LCMS calc.=596.98; found=598.05 (M+1)+. 132.6 mg of unreacted starting material was also recovered.

Workup

  1. temperaturecooled in an ice bath
  2. customquenched
  3. additionadding by NH4Cl (aq, sat.) when reaction time
  4. waitwas 5 hours
  5. customReaction crude
  6. extractionwas extracted with ethyl acetate
  7. dry with materialThe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated to an oil
  10. customThe oil was purified by flash chromatography (SiO2, Biotage 40+M cartridge, EtOAc/hexanes)

Sources & evidence

ORD record
ord-7048404acc94430892f774b4523d12dd
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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