Aluminum(III) Chloride → 6-hydroxy-1-isopropyl-1H-indole-4-carboxylic acid methyl ester

HRID 873471Notes

Reaction equation

HRID 873471 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[CH:8][N:9]([CH:16]([CH3:18])[CH3:17])[C:10]=2[CH:11]=[C:12]([O:14]C)[CH:13]=1)=[O:4].[Cl-].[Al+3].[Cl-].[Cl-]>C1(C)C=CC=CC=1.O>[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[CH:8][N:9]([CH:16]([CH3:18])[CH3:17])[C:10]=2[CH:11]=[C:12]([OH:14])[CH:13]=1)=[O:4]

Participants

5

Reactant 2

HCID 6451240Aluminum(III) ChlorideHCID 674645681-isopropyl-6-methoxy-1H-indole-4-carboxylic acid methyl ester

Product 1

HCID 674654646-hydroxy-1-isopropyl-1H-indole-4-carboxylic acid methyl esterYield 83.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

To a stirred solution of 1-isopropyl-6-methoxy-1H-indole-4-carboxylic acid methyl ester (1.9 g, 7.69 mmol) in toluene (20 mL) was added anhydrous aluminum chloride (5.11 g, 38.4 mmol) at room temperature and then heated to reflux for 2 h. The reaction mixture was diluted with water and extracted with ethyl acetate (2×20 mL). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography by eluting 3-15% Ethyl acetate in petroleum ether to afford the title compound 6-hydroxy-1-isopropyl-1H-indole-4-carboxylic acid methyl ester (1.5 g, 83%) as yellow colored gum. 1H NMR (400 MHz, DMSO-d6): δ 1.43 (d, J=6.8 Hz, 6H), 3.86 (s, 3H), 4.65-4.61 (m, 1H), 6.81 (d, J=2.8 Hz, 1H), 7.11 (s, 1H), 7.29 (s, 1H), 7.44 (d, J=2.8 Hz, 1H), 9.32 (bs, 1H). LCMS (ES+): m/z=234.09 [M+H]

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 h
  3. extractionextracted with ethyl acetate (2×20 mL)
  4. dry with materialThe combined organic layer was dried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography
  7. washby eluting 3-15% Ethyl acetate in petroleum ether

Sources & evidence

ORD record
ord-6502c79049614d9099e7ba6440b8e0b2
Source dataset
uspto-grants-2015_03
Patent number
US08975291B2

Reaction notes

Loading…