Hydrogen Bromide → 2-Methyl-1H-indol-6-ol

HRID 1663642Notes

Reaction equation

HRID 1663642 reaction equation
C[O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([CH3:12])[NH:9]2)=[CH:5][CH:4]=1.Br>C(O)(=O)C>[CH3:12][C:8]1[NH:9][C:10]2[C:6]([CH:7]=1)=[CH:5][CH:4]=[C:3]([OH:2])[CH:11]=2

Participants

4

Reactant 2

HCID 260Hydrogen BromideHCID 108447096-methoxy-2-methyl-1H-indole

Product 1

HCID 148785962-Methyl-1H-indol-6-olYield 65.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a suspension of lithium aluminum hydride (3.7 g, 97 mmol) in 1,4-dioxane (97 mL) was slowly added dropwise a solution of methyl 6-methoxy-1H-indole-2-carboxylate (2.0 g, 9.8 mmol) in 1,4-dioxane (30 mL) under ice-cooling. After dropwise addition, the reaction mixture was heated under reflux for 24 hr. A saturated aqueous sodium sulfate solution was added to the mixture under cooling, magnesium sulfate was added and the insoluble material was filtrated. The filtrate was concentrated under reduced pressure, and the residue was recrystallized from hexane to give 6-methoxy-2-methyl-1H-indole (1.0 g, 6.5 mmol) as a yellow solid. To a solution of 6-methoxy-2-methyl-1H-indole (1.0 g, 6.2 mmol) in acetic acid (15 mL) was added 48% aqueous hydrogen bromide (31 mL) at room temperature, and the reaction mixture was heated under reflux for 3 hr. The solvent was evaporated under reduced pressure, ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogencarbonate solution were added to the residue. The aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×3). Combined organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and filtrated. The filtrate was concentrated under reduced pressure, and the residue was washed with ethyl acetate/hexane to give the title compound (600 mg, 65%) as a white solid.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureunder reflux for 3 hr
  3. customThe solvent was evaporated under reduced pressure, ethyl acetate/tetrahydrofuran and saturated aqueous sodium hydrogencarbonate solution
  4. additionwere added to the residue
  5. extractionThe aqueous layer was extracted with ethyl acetate/tetrahydrofuran (×3)
  6. washCombined organic layer was washed with saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltrated
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. washthe residue was washed with ethyl acetate/hexane

Sources & evidence

ORD record
ord-712af53bb9c244ecb025256f60eb1c44
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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