Hydrochloric Acid → 2-methyl-4-(trifluoromethyl)-1H-indole

HRID 2278642Notes

Reaction equation

HRID 2278642 reaction equation
[OH-].[Na+].C1(S([N:12]2[C:20]3[C:15](=[C:16]([C:21]([F:24])([F:23])[F:22])[CH:17]=[CH:18][CH:19]=3)[CH:14]=[C:13]2[CH3:25])(=O)=O)C=CC=CC=1.O.Cl>C(O)C.C(COC)OC>[CH3:25][C:13]1[NH:12][C:20]2[C:15]([CH:14]=1)=[C:16]([C:21]([F:23])([F:22])[F:24])[CH:17]=[CH:18][CH:19]=2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 578003011-benzenesulfonyl-2-methyl-4-trifluoromethyl-1H-indole

Product 1

HCID 196970222-methyl-4-(trifluoromethyl)-1H-indoleYield 79.3%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

0.271 ml of 5N sodium hydroxide is added to a solution of 460 mg of 1-benzenesulfonyl-2-methyl-4-trifluoromethyl-1H-indole in 1.4 ml of ethanol and 0.44 ml of dimethoxyethane. The reaction mixture is maintained at reflux for 6 hours and poured into water acidified with a hydrochloric acid solution until pH=1 and extracted with ethyl acetate. The organic phases are combined and washed with a 10% sodium bicarbonate solution and a saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica column chromatography, elution being carried out with a mixture of heptane and diisopropyl ether (98/2, then 95/5: v/v), so as to give 214 mg of 2-methyl-4-trifluoromethyl-1H-indole, in the form of a pale yellow oil, which is used in the next step.

Workup

  1. temperatureThe reaction mixture is maintained
  2. temperatureat reflux for 6 hours
  3. extractionextracted with ethyl acetate
  4. washwashed with a 10% sodium bicarbonate solution
  5. dry with materiala saturated sodium chloride solution, dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is purified by silica column chromatography, elution
  9. additionbeing carried out with a mixture of heptane and diisopropyl ether (98/2

Sources & evidence

ORD record
ord-5db36a8150574ea1aa3fded95a06258f
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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