Sodium hydride → 3-[2-Iodo-5-(trifluoromethyl)benzyl]-6-phenyl-1,3-oxazinan-2-one

HRID 537952Notes

Reaction equation

HRID 537952 reaction equation
[H-].[Na+].[C:3]1([CH:9]2[O:14][C:13](=[O:15])[NH:12][CH2:11][CH2:10]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Br[CH2:17][C:18]1[CH:23]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:21]=[CH:20][C:19]=1[I:28].[NH4+].[Cl-]>C1COCC1>[I:28][C:19]1[CH:20]=[CH:21][C:22]([C:24]([F:25])([F:26])[F:27])=[CH:23][C:18]=1[CH2:17][N:12]1[CH2:11][CH2:10][CH:9]([C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[O:14][C:13]1=[O:15]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 2410056-Phenyl-1,3-oxazinan-2-oneHCID 184515342-(Bromomethyl)-1-iodo-4-(trifluoromethyl)benzene2×

Product 1

HCID 575443563-[2-Iodo-5-(trifluoromethyl)benzyl]-6-phenyl-1,3-oxazinan-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A stirred and cooled (0° C.) suspension of sodium hydride (60% suspension in mineral oil, 14 mg, 0.34 mmol) in THF (2 mL) was treated dropwise with a solution of 6-phenyl-1,3-oxazinan-2-one (24 mg, 0.137 mmol) in THF (2 mL), under an atmosphere of nitrogen. The reaction was stirred for 20 min at 0° C. and 2-(bromomethyl)-1-iodo-4-(trifluoromethyl)benzene (Intermediate 11; 50 mg, 0.137 mmol) was added. The reaction was allowed to warm to room temperature and stirred for an additional 3 h. Saturated NH4Cl (1 mL) was added and the resultant mixture was partitioned between H2O (20 mL) and EtOAC (20 mL). The aqueous layer was re-extracted with EtOAc (3×20 mL) and the combined extracts were washed with brine (40 mL), dried (Na2SO4), filtered and concentrated in vacuo to afford 3-[2-iodo-5-(trifluoromethyl)benzyl]-6-phenyl-1,3-oxazinan-2-one as a colorless oil. LCMS=462.0 (M+1)+.

Workup

  1. temperaturecooled
  2. stirringThe reaction was stirred for 20 min at 0° C.
  3. stirringstirred for an additional 3 h
  4. customthe resultant mixture was partitioned between H2O (20 mL) and EtOAC (20 mL)
  5. extractionThe aqueous layer was re-extracted with EtOAc (3×20 mL)
  6. washthe combined extracts were washed with brine (40 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-25226ab5153d443da87d06cac24020e7
Source dataset
uspto-grants-2014_10
Patent number
US08865707B2

Reaction notes

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