Sodium Hydroxide → 6-bromo-1-cyclopropyl-1H-indole-4-carboxylic acid

HRID 593891Notes

Reaction equation

HRID 593891 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C:14]([O:16]C)=[O:15])[C:5]2[CH:6]=[CH:7][N:8]([CH:11]3[CH2:13][CH2:12]3)[C:9]=2[CH:10]=1.[OH-].[Na+]>CO.C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([C:14]([OH:16])=[O:15])[C:5]2[CH:6]=[CH:7][N:8]([CH:11]3[CH2:13][CH2:12]3)[C:9]=2[CH:10]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 67467490methyl 6-bromo-1-cyclopropyl-1H-indole-4-carboxylate

Product 1

HCID 674651346-bromo-1-cyclopropyl-1H-indole-4-carboxylic acidYield 90%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 6-bromo-1-cyclopropyl-1H-indole-4-carboxylate (0.43 g, 1.462 mmol) in MeOH (12 mL) and THF (3 mL) was added 3M NaOH (1.949 mL, 5.85 mmol). The reaction was stirred for 18 h at RT, at which time the volatiles were removed in vacuo. The residue was diluted with water and slowly acidified with 1N HCl to pH 4-5, then extracted with EtOAc (2×). The combine organics were wash with brine, dried over magnesium sulfate, filtered, and concentrated to give 6-bromo-1-cyclopropyl-1H-indole-4-carboxylic acid (0.376 g, 1.315 mmol, 90% yield) as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.92-1.01 (m, 2H) 1.05-1.12 (m, 2H) 3.51 (tt, J=7.07, 3.66 Hz, 1H) 6.89 (d, J=2.53 Hz, 1H) 7.52 (d, J=3.03 Hz, 1H) 7.80 (d, J=1.77 Hz, 1H) 7.99 (d, J=1.01 Hz, 1H) 13.05 (br. s., 1H). MS(ES) [M+H]+ 280.1.

Workup

  1. customwere removed in vacuo
  2. additionThe residue was diluted with water
  3. extractionextracted with EtOAc (2×)
  4. washThe combine organics were wash with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-8aa2b945e15e464299529e263658ff06
Source dataset
uspto-grants-2016_01
Patent number
US09242962B2

Reaction notes

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