Methyl iodide → 6-bromo-3,3-dimethyl-2,3-dihydro-1H-indol-2-one

HRID 1507561Notes

Reaction equation

HRID 1507561 reaction equation
CC([O-:5])(C)C.[K+].[Br:7][C:8]1[CH:16]=[C:15]2[C:11](CC(=O)[NH:14]2)=[CH:10][CH:9]=1.CI.[Cl-].[NH4+].CO[C:24]([CH3:27])([CH3:26])[CH3:25]>C1COCC1.O>[Br:7][C:8]1[CH:16]=[C:15]2[C:11]([C:24]([CH3:25])([CH3:26])[C:27](=[O:5])[NH:14]2)=[CH:10][CH:9]=1

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 15413tert-Butyl methyl etherHCID 25517Ammonium ChlorideHCID 27732896-bromo-2,3-dihydro-1H-indol-2-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 106576496-bromo-3,3-dimethyl-2,3-dihydro-1H-indol-2-one

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of potassium tert-butylate (12.8 g, 114 mmol) in dry THF (80 ml) at 0° C. under an argon atmosphere was added portionwise 6-bromoindolin-2-one (5.0 g, 22.9 mmol) followed by copper(I) bromide-dimethylsulfide complex (470 mg, 2.29 mmol). MeI (6.82 g, 3.00 ml, 48.0 mmol) was added dropwise within 45 minutes, keeping temperature of the reaction mixture below 8° C. The reaction mixture was warmed to room temperature and kept at this temperature for 16 hours. The reaction mixture was cooled to 0° C. again and saturated aqueous ammonium chloride solution was cautiously added. The mixture was diluted with tert-butyl methyl ether and water. The aqueous phase was extracted with tert-butyl methyl ether, the combined organic phases were dried over sodium sulfate, the solvent was evaporated and the residue purified by silica gel chromatography using ethyl acetate/heptane as eluent. The title compound was obtained as light yellow solid (5.17 g).

Workup

  1. customtemperature of the reaction mixture below 8° C
  2. temperatureThe reaction mixture was cooled to 0° C. again
  3. extractionThe aqueous phase was extracted with tert-butyl methyl ether
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. customthe solvent was evaporated
  6. customthe residue purified by silica gel chromatography

Sources & evidence

ORD record
ord-bd5fad5eede5496fb0f6954d13438288
Source dataset
uspto-grants-2015_12
Patent number
US09221816B2

Reaction notes

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