Hydrochloric Acid → 6-Methoxy-1-methyl-2-trifluoromethyl-1H-indole-3-carboxylic acid

HRID 1825171Notes

Reaction equation

HRID 1825171 reaction equation
C([O:3][C:4]([C:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][CH3:16])=[CH:12][CH:13]=2)[N:8]([CH3:17])[C:7]=1[C:18]([F:21])([F:20])[F:19])=[O:5])C.[OH-].[K+].Cl>C1COCC1.CO.O>[CH3:16][O:15][C:11]1[CH:10]=[C:9]2[C:14]([C:6]([C:4]([OH:5])=[O:3])=[C:7]([C:18]([F:20])([F:21])[F:19])[N:8]2[CH3:17])=[CH:13][CH:12]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 207678746-Methoxy-1-methyl-2-trifluoromethyl-1H-indole-3-carboxylic acid Ethyl Ester

Product 1

HCID 221435206-Methoxy-1-methyl-2-trifluoromethyl-1H-indole-3-carboxylic acidYield 65%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 6-methoxy-1-methyl-2-trifluoromethyl-1H-indole-3-carboxylic acid ethyl ester 76e (1.5 g, 4.98 mmole) in 10 ml THF and 5 ml MeOH was added a solution of KOH (2.8 g, 50 mmole) in 5 ml water with ice bath cooling. The mixture was warmed to room temperature and stirred overnight. Concentrated aqueous HCl solution was added to adjust the pH to 1. The mixture was extracted with EtOAc and the combined organic layer was dried over Na2SO4, filtered and concentrated. The residue was further purified by column chromatography (eluting with 1–5% MeOH in CH2Cl2) to give 880 mg product (65% yield). 1H NMR (300 MHz, CD3OD) δ 7.90 (1H, d, J=9.0 Hz), 7.01 (1H, d, J=2.1 Hz), 6.91 (1H, dd, J=2.1, 9.0 Hz), 3.90 (3H, s), 3.88 (3H, s).

Workup

  1. temperaturecooling
  2. extractionThe mixture was extracted with EtOAc
  3. dry with materialthe combined organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was further purified by column chromatography (eluting with 1–5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-9a0c167d2beb4533b68f4869bfb805a3
Source dataset
uspto-grants-2006_05
Patent number
US07045528B2

Reaction notes

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