Methyl iodide → 1-benzenesulfonyl-2-methyl-4-trifluoromethyl-1H-indole

HRID 2278641Notes

Reaction equation

HRID 2278641 reaction equation
[CH2:1]([Li])CCC.C(NC(C)C)(C)C.[C:13]1([S:19]([N:22]2[C:30]3[C:25](=[C:26]([C:31]([F:34])([F:33])[F:32])[CH:27]=[CH:28][CH:29]=3)[CH:24]=[CH:23]2)(=[O:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CI.[Cl-].[NH4+]>O1CCCC1>[C:13]1([S:19]([N:22]2[C:30]3[C:25](=[C:26]([C:31]([F:33])([F:34])[F:32])[CH:27]=[CH:28][CH:29]=3)[CH:24]=[C:23]2[CH3:1])(=[O:21])=[O:20])[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

7

Reactant 5

HCID 6328Methyl iodide2×HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 578003941-benzenesulfonyl-4-trifluoromethyl-1H-indoleHCID 178418339Butyllithium

Product 1

HCID 578003011-benzenesulfonyl-2-methyl-4-trifluoromethyl-1H-indole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

3 ml of n-butyllithium (1.6M in hexane) are added dropwise to a solution of 0.7 ml of diisopropylamine in 10 ml of tetrahydrofuran under argon at −30° C. The solution is stirred for 30 min at ambient temperature, and cooled to −60° C. and a solution of 1.07 g of 1-benzenesulfonyl-4-trifluoromethyl-1H-indole in 10 ml of tetrahydrofuran is added dropwise. The reaction medium is brought back up to ambient temperature and then taken back to −60° C. in order to add, dropwise, 0.31 ml of methyl iodide. After addition, the mixture is allowed to come back up to 0° C. with stirring for 10 minutes, and then to 10° C. for 10 min, before adding a further 0.3 ml of methyl iodide. After returning to ambient temperature, the reaction mixture is stirred for 1 h 30 and then poured into a 10% ammonium chloride solution and extracted with ethyl acetate. The organic phases are washed with 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 476 mg of 1-benzenesulfonyl-2-methyl-4-trifluoromethyl-1H-indole, in the form of an oil, which is used in the next step.

Workup

  1. temperaturecooled to −60° C.
  2. customis brought back up to ambient temperature
  3. customtaken back to −60° C. in order
  4. additionto add
  5. additionAfter addition
  6. customto come back up to 0° C.
  7. stirringwith stirring for 10 minutes
  8. waitto 10° C. for 10 min
  9. customAfter returning to ambient temperature
  10. stirringthe reaction mixture is stirred for 1 h 30
  11. extractionextracted with ethyl acetate
  12. washThe organic phases are washed with a saturated sodium chloride solution
  13. dry with materialdried over magnesium sulfate
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure
  16. customThe residue is purified by silica column chromatography, elution
  17. additionbeing carried out with a mixture of heptane and diisopropyl ether (98/2

Sources & evidence

ORD record
ord-37bea7b9fbc64143ba7944da1fbcf3ff
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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