Hydrochloric Acid → 6-bromo-1-(1-methylethyl)-1H-indole-4-carboxylic acid

HRID 62401Notes

Reaction equation

HRID 62401 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]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.[OH-].[Na+].Cl>CO.O1CCCC1.O>[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]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 67466539methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylate

Product 1

HCID 674686386-bromo-1-(1-methylethyl)-1H-indole-4-carboxylic acidYield 99%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 6-bromo-1-(1-methylethyl)-1H-indole-4-carboxylate (0.52 g, 1.756 mmol) in methanol (15 mL) and tetrahydrofuran (3 mL) was added 3 M NaOH (1.756 mL, 5.27 mmol) via syringe drop wise (over 2 min). The solution was maintained at RT for 2 h, at which time LCMS showed only 12% conversion to product. Then 1.5 mL 3 M NaOH was added and the solution was maintained at RT overnight. LCMS showed complete conversion to product. Removed volatiles in vacuo and dissolved the residue in water and slowly acidified with 1 M HCl (solids precipitated). Extracted with EtOAc (2×), combined organics and dried over MgSO4. Filtered and concentrated in vacuo to give 6-bromo-1-(1-methylethyl)-1H-indole-4-carboxylic acid (0.50 g, 1.737 mmol, 99% yield) as a white solid.

Workup

  1. temperaturethe solution was maintained at RT overnight
  2. extractionExtracted with EtOAc (2×)
  3. dry with materialdried over MgSO4
  4. filtrationFiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7c467e347d8f4e17bb03d841347ec3a2
Source dataset
uspto-grants-2016_09
Patent number
US09446041B2

Reaction notes

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