Methyl iodide → 6-Bromo-5-fluoro-1,2,2-trimethylindolin-3-one

HRID 331053Notes

Reaction equation

HRID 331053 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](=[O:13])[C:7]([CH3:12])([CH3:11])[NH:8]2)=[CH:4][C:3]=1[F:14].[H-].[Na+].I[CH3:18]>CN(C=O)C>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](=[O:13])[C:7]([CH3:11])([CH3:12])[N:8]2[CH3:18])=[CH:4][C:3]=1[F:14]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 710896586-Bromo-5-fluoro-2,2-dimethylindolin-3-one

Product 1

HCID 710901506-Bromo-5-fluoro-1,2,2-trimethylindolin-3-oneYield 97.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-bromo-5-fluoro-2,2-dimethylindolin-3-one (D90) (240 mg, 0.930 mmol) in DMF (3 mL) at 0° C. was added sodium hydride (55.8 mg, 1.395 mmol). After stirring for 10 min, iodomethane (0.116 mL, 1.860 mmol) was added to the mixture and the mixture was stirred for 30 min at 0° C. The reaction was quenched with addition of saturated NH4Cl (1 mL) and the mixture was poured into water (60 mL). The mixture was extracted with ethyl acetate (10 mL×3). The organic layers were combined, washed with brine (50 mL), dried over MgSO4, filtered and evaporated in vacuo. The crude residue was purified by chromatography on silica, eluting with a gradient of 0-30% ethyl acetate in cyclohexane to give the title compound (247.7 mg). LCMS (A): m/z (M+H)+ 272/274, C11H11BrFNO requires 271/273 (acidic).

Workup

  1. stirringthe mixture was stirred for 30 min at 0° C
  2. customThe reaction was quenched with addition of saturated NH4Cl (1 mL)
  3. additionthe mixture was poured into water (60 mL)
  4. extractionThe mixture was extracted with ethyl acetate (10 mL×3)
  5. washwashed with brine (50 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe crude residue was purified by chromatography on silica
  10. washeluting with a gradient of 0-30% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-f9551c380d204e81a644f15ee2cf771b
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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