Sodium Hydroxide → 6-Bromo-5-fluoro-2,2-dimethylindolin-3-one

HRID 331052Notes

Reaction equation

HRID 331052 reaction equation
C([N:4]1[C:12]2[C:7](=[CH:8][C:9]([F:14])=[C:10]([Br:13])[CH:11]=2)[C:6](=[O:15])[C:5]1([CH3:17])[CH3:16])(=O)C.[OH-].[Na+]>C(O)C>[Br:13][C:10]1[CH:11]=[C:12]2[C:7]([C:6](=[O:15])[C:5]([CH3:16])([CH3:17])[NH:4]2)=[CH:8][C:9]=1[F:14]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 710896451-Acetyl-6-bromo-5-fluoro-2,2-dimethylindolin-3-one

Product 1

HCID 710896586-Bromo-5-fluoro-2,2-dimethylindolin-3-oneYield 95.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 1-acetyl-6-bromo-5-fluoro-2,2-dimethylindolin-3-one (D89) (297 mg, 0.990 mmol) in ethanol (3 mL) was added 2M aqueous sodium hydroxide (0.594 mL, 1.188 mmol) and the mixture was heated at 90° C. for 1 h. After cooling to RT, ethanol was evaporated in vacuo. Aqueous residue was poured into water (10 mL) and extracted with ethyl acetate (10 mL×3). The organic layers were combined, washed with brine (10 mL), dried over MgSO4, filtered and evaporated in vacuo. The crude residue was purified by chromatography on silica, eluting with a gradient of 0-40% ethyl acetate in cyclohexane to give title compound (244.1 mg). LCMS (A): m/z (M+H)+ 258/260, C10H9BrFNO requires 257/259 (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. customethanol was evaporated in vacuo
  3. additionAqueous residue was poured into water (10 mL)
  4. extractionextracted with ethyl acetate (10 mL×3)
  5. washwashed with brine (10 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 0-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-162d7a63df0b46d190245f186e7433de
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

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