Water → 1-methyl-2-trifluoromethyl-1H-indole-5-carbonitrile

HRID 2061567Notes

Reaction equation

HRID 2061567 reaction equation
[H-].[Na+].[F:3][C:4]([F:17])([F:16])[C:5]1[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][C:10]([C:14]#[N:15])=[CH:9][CH:8]=2.I[CH3:19].O>CN(C=O)C>[CH3:19][N:6]1[C:7]2[C:12](=[CH:11][C:10]([C:14]#[N:15])=[CH:9][CH:8]=2)[CH:13]=[C:5]1[C:4]([F:3])([F:16])[F:17]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 581268122-(trifluoromethyl)-1H-indole-5-carbonitrile2×

Product 1

HCID 581268251-methyl-2-trifluoromethyl-1H-indole-5-carbonitrileYield 135.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in mineral oil) (76 mg, 1.903 mmol) was added to 2-trifluoromethyl-1H-indole-5-carbonitrile (Intermediate 3, 200 mg, 0.952 mmol) stirred in DMF (5 mL) under argon at room temperature. The reaction mixture was stirred at room temperature for 30 min and iodomethane (0.119 mL, 1.903 mmol) was then added. The reaction mixture was left to stir for a further 1 h. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (50 mL). The organic extract was washed with 1:1 water: Brine (50 mL×2), dried (MgSO4), filtered and the solvent removed to give the title compound (290 mg) which was then used in the next reaction without further purification; 1H NMR (400 MHz, CDCl3): δ 8.05 (1H, d), 7.59 (1H, dd), 7.46 (1H, d), 7.03 (1H, s), 3.90 (3H, s); m/z 225 (M+H).

Workup

  1. waitThe reaction mixture was left
  2. stirringto stir for a further 1 h
  3. extractionextracted with ethyl acetate (50 mL)
  4. extractionThe organic extract
  5. washwas washed with 1:1 water
  6. dry with materialBrine (50 mL×2), dried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent removed

Sources & evidence

ORD record
ord-48d554eaed1f4870b54872ba18cd6529
Source dataset
uspto-grants-2012_10
Patent number
US08283365B2

Reaction notes

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