Sodium hydride → HCID 57809957, compound

HRID 2106048Notes

Reaction equation

HRID 2106048 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=[O:10].[H-].[Na+].[H][H].[F:15][C:16]1[CH:17]=[CH:18][C:19]([O:33][CH3:34])=[C:20]([C:22]([CH3:32])([CH3:31])[CH2:23][C:24]2([C:27]([F:30])([F:29])[F:28])[CH2:26][O:25]2)[CH:21]=1>CN(C=O)C.[Cl-].[NH4+]>[F:15][C:16]1[CH:17]=[CH:18][C:19]([O:33][CH3:34])=[C:20]([C:22]([CH3:31])([CH3:32])[CH2:23][C:24]([OH:25])([C:27]([F:30])([F:29])[F:28])[CH2:26][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH2:3][C:2]2=[O:10])[CH:21]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 321710OxindoleHCID 160992392-[2-(5-Fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxiraneHCID 178418361HCID 178418361, compound

Product 1

HCID 57809957HCID 57809957, compoundYield 19.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
75 °C

Procedure

To a solution of 42 mg (0.31 mmol) of oxindole in 1 mL of DMF was added 10 mg (0.39 mmol) of 60% sodium hydride in mineral oil. After hydrogen evolution ceased, 50 mg (0.17 mmol) of 2-[2-(5-fluoro-2-methoxyphenyl)-2-methylpropyl]-2-trifluoromethyloxirane was added and the mixture was warmed to 75° C. The reaction was monitored by TLC (ethyl acetate-hexanes (15:85)). After 40 minutes, the mixture was cooled and diluted with saturated aqueous ammonium chloride and extracted with three 5 mL portions of ethyl acetate. The combined organic layers were washed with three 5 mL portions of brine, dried over magnesium sulfate, and concentrated in vacuo. The crude material was chromatographed on silica gel prep plates (2×1 mm, ethyl acetate-hexanes (15:85)). The material from the prep plate was recrystallized from dichloromethane-hexanes-ether to afford 14 mg of the title compound.

Workup

  1. temperaturethe mixture was cooled
  2. extractionextracted with three 5 mL portions of ethyl acetate
  3. washThe combined organic layers were washed with three 5 mL portions of brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe crude material was chromatographed on silica gel prep plates (2×1 mm, ethyl acetate-hexanes (15:85))
  7. customThe material from the prep plate was recrystallized from dichloromethane-hexanes-ether

Sources & evidence

ORD record
ord-891dad0dafaa497aa5fb11ad1edc18d3
Source dataset
uspto-grants-2009_08
Patent number
US07579469B2

Reaction notes

Loading…