Water → 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid

HRID 1477041Notes

Reaction equation

HRID 1477041 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:15]([O:17]C)=[O:16])[C:5]2[C:6]([CH3:14])=[CH:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[OH-].[Na+].O>C(O)C>[Br:1][C:2]1[CH:3]=[C:4]([C:15]([OH:17])=[O:16])[C:5]2[C:6]([CH3:14])=[CH:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1

Participants

5

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 67464634methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylate

Product 1

HCID 674686786-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acidYield 89.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of methyl 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylate (24 g, 77.4 mmol) in ethanol (400 mL) was added sodium hydroxide (4.02 g, 100.6 mmol), water (11 mL) and the mixture was stirred at reflux condition for 6 h. Ethanol was distilled off and residue was diluted with water, extracted with ethylacetate (40 mL) adjusted aqueous layer to PH-3 with 1N HCl and extracted with ethyl acetate (3×250 mL), finally organic layer was washed with brine solution, dried over anhydrous Na2SO4 and concentrated. The crude was washed with pet ether, filtered the solid and dried to afford desired product 6-bromo-1-isopropyl-3-methyl-1H-indole-4-carboxylic acid (20.6 g, 89.8%). 1H NMR (DMSO-d6, 400 MHz): δ 1.407 (d, J=6.4 Hz, 6H), 2.296 (s, 3H), 4.754-4.819 (m, 1H), 7.455 (s, 1H), 7.472 (s, 1H), 7.938 (s, 1H), 12.950 (brs, 1H). LCMS (ES+) m/z=296.15 (M+H).

Workup

  1. temperatureat reflux condition for 6 h
  2. distillationEthanol was distilled off
  3. additionresidue was diluted with water
  4. extractionextracted with ethylacetate (40 mL)
  5. extractionextracted with ethyl acetate (3×250 mL), finally organic layer
  6. washwas washed with brine solution
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated
  9. washThe crude was washed with pet ether
  10. filtrationfiltered the solid
  11. customdried

Sources & evidence

ORD record
ord-5d5ec780c11e438eb94d6df397c8907c
Source dataset
uspto-grants-2016_08
Patent number
US09402836B2

Reaction notes

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