5-Methoxy-1-benzylindoline → 1-Benzylindolin-5-ol

HRID 2360118Notes

Reaction equation

HRID 2360118 reaction equation
C[O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:7][CH2:6]2.Br.C(O)(=O)C>C([O-])(O)=O.[Na+]>[CH2:12]([N:8]1[C:9]2[C:5](=[CH:4][C:3]([OH:2])=[CH:11][CH:10]=2)[CH2:6][CH2:7]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 111181425-Methoxy-1-benzylindolineHCID 21893785Acetic Acid Mixture with Hydrobromic Acid

Product 1

HCID 866598571-Benzylindolin-5-olYield 93.2%

Reagents, catalysts & solvents 1

HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of 5-methoxyindole (147 mg, 1.00 mmol) in 2.5 mL of tetrahydrofuran was added acetic acid (2.5 mL) and sodium cyanoborohydride (220 mg, 3.50 mmol) at room temperature. After the reaction mixture was stirred at the same temperature for 20 min, benzaldehyde (0.20 mL, 2.0 mmol) was added with additional stirring for 1 h. After the reaction mixture was diluted with water (20 mL) and a 1:1 solution (20 mL) of hexane and ethyl acetate, the aqueous layer was extracted with a 1:1 solution (20 mL) of hexane and ethyl acetate. The combined extracts were washed with saturated NaHCO3 aqueous solution, brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=90/10 to 80/20) to obtain 5-methoxy-1-benzylindoline (158 mg, 66%) as a sticky oil. To 5-methoxy-1-benzylindoline (4.30 g, 18.0 mmol) was added a solution of 50% hydrogen bromide-acetic acid solution (90 mL) at room temperature. After the reaction mixture was stirred at 115° C. for 22 h, the reaction mixture was neutralized by saturated NaHCO3 aqueous solution (200 mL) and the solution was extracted with ethyl acetate (200 mL) twice. The combined extracts were washed with brine, and dried over MgSO4. After filtration, the filtrate was concentrated in vacuo, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20 to 70/30) to obtain the title compound (3.78 g, 93%) as a sticky oil.

Workup

  1. extractionthe solution was extracted with ethyl acetate (200 mL) twice
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated in vacuo
  6. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate=80/20 to 70/30)

Sources & evidence

ORD record
ord-4da9e9dd1b19461991827effbd15239a
Source dataset
uspto-grants-2014_04
Patent number
US08686024B2

Reaction notes

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