Sulfuric acid magnesium salt (1:1) → 6-methoxy-2-methyl-1H-indole

HRID 1663641Notes

Reaction equation

HRID 1663641 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH3:7][O:8][C:9]1[CH:17]=[C:16]2[C:12]([CH:13]=[C:14]([C:18](OC)=O)[NH:15]2)=[CH:11][CH:10]=1.S([O-])([O-])(=O)=O.[Na+].[Na+].S([O-])([O-])(=O)=O.[Mg+2]>O1CCOCC1>[CH3:7][O:8][C:9]1[CH:17]=[C:16]2[C:12]([CH:13]=[C:14]([CH3:18])[NH:15]2)=[CH:11][CH:10]=1

Participants

6

Reactant 4

HCID 24083Sulfuric acid magnesium salt (1:1)HCID 24436Sodium SulfateHCID 688173Methyl-6-methoxy-2-indolecarboxylateHCID 21226445Aluminium lithium hydride

Product 1

HCID 108447096-methoxy-2-methyl-1H-indoleYield 66.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

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. temperaturecooling
  2. additionAfter dropwise addition
  3. temperaturethe reaction mixture was heated
  4. temperatureunder reflux for 24 hr
  5. temperatureunder cooling
  6. filtrationthe insoluble material was filtrated
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe residue was recrystallized from hexane

Sources & evidence

ORD record
ord-e5e366fd3fd048fda01f6d2e0fd150f6
Source dataset
uspto-grants-2011_10
Patent number
US08034812B2

Reaction notes

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