Bromine → 5-bromo-1-methyl-2-oxo-2,3-dihydro-1H-indole-6-carbonitrile

HRID 1623544Notes

Reaction equation

HRID 1623544 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[CH2:4][C:3]1=[O:13].[Br-:14].[K+].BrBr>O.ClCCl.C(=O)(O)[O-].[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>[Br:14][C:7]1[CH:6]=[C:5]2[C:10](=[CH:9][C:8]=1[C:11]#[N:12])[N:2]([CH3:1])[C:3](=[O:13])[CH2:4]2

Participants

8

Reactant 3

HCID 24408Bromine2×HCID 253877Potassium BromideHCID 667883311-methyl-2-oxo-2,3-dihydro-1H-indole-6-carbonitrile2×

Product 1

HCID 667939935-bromo-1-methyl-2-oxo-2,3-dihydro-1H-indole-6-carbonitrile

Reagents, catalysts & solvents 4

HCID 962WaterSolvent3×HCID 6344DichloromethaneSolventHCID 24477Sodium ThiosulfateSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
70 °C

Procedure

Water (9 mL) was added to 1-methyl-2-oxo-2,3-dihydro-1H-indole-6-carbonitrile (110 mg 0.64 mmol) and the resulting mixture was placed at 70° C. In a separate flask potassium bromide (462 g, 0.26 mmol) in water (12 mL) was treated with bromine (0.100 mL, 1.94 mmol). 6.0 mL of the orange bromine solution was added dropwise to the water and 1-methyl-2-oxo-2,3-dihydro-1H-indole-6-carbonitrile mixture over ca. 20 minutes. The resulting heterogeneous mixture was permitted to stir at 70° C. for an additional 5 minutes and then cooled to room temperature. The reaction was then diluted with dichloromethane and saturated aqueous sodium bicarbonate. The solution was then further diluted with saturated aqueous sodium thiosulfate. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic extracts were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane 0 to 3.5%) to provide 5-bromo-1-methyl-2-oxo-2,3-dihydro-1H-indole-6-carbonitrile; MS: (ES+) m/z 250.9 (M+H)+.

Workup

  1. customwas placed at 70° C
  2. temperaturecooled to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted two additional times with dichloromethane
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by silica gel flash chromatography (ethanol-dichloromethane 0 to 3.5%)

Sources & evidence

ORD record
ord-7ff628001fe24a09a84ac4c8cfef953b
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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