Methanol → 1-[(1R)-1-Methyl-2-(methylsulfonyl)ethyl]-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 1851119Notes

Reaction equation

HRID 1851119 reaction equation
CS[CH2:3][C@H:4]([N:6]1[C:14]2[C:9](=[C:10]([C:17]([F:20])([F:19])[F:18])[C:11]([C:15]#[N:16])=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)[CH3:5].O[O:22][S:23]([O-:25])=O.[K+].[CH3:27]O>O>[CH3:27][S:23]([CH2:5][C@H:4]([N:6]1[C:14]2[C:9](=[C:10]([C:17]([F:19])([F:18])[F:20])[C:11]([C:15]#[N:16])=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)[CH3:3])(=[O:25])=[O:22]

Participants

5

Reactant 3

HCID 887MethanolHCID 23707502Potassium hydroxy sulfiteHCID 86709175HCID 86709175, compound

Product 1

HCID 867091741-[(1R)-1-Methyl-2-(methylsulfonyl)ethyl]-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To an ice-cold solution of (R)-1-(1-(methylthio)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile (0.560 g, 1.88 mmol) in MeOH (10 mL) was added a solution of Oxone (4.04 g, 6.57 mmol) in water (10 mL). After 50 min, the reaction mixture was diluted with water (30 mL) and extracted with EtOAc (50 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was chromatographed over silica gel using 100% CH2Cl2 to give (R)-1-(1-(methylsulfonyl)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile as a white foam that was crystallized from CH2Cl2/hexanes to afford a white solid (0.508 g, 79% yield): 1H NMR (400 MHz, DMSO-d6) δ 8.17 (d, J=8.6 Hz, 1H), 8.12 (d, J=3.5 Hz, 1H), 7.81 (d, J=8.5 Hz, 1H), 6.87-6.84 (m, 1H), 5.43-5.35 (m, 1H), 4.01 (dd, J=14.8, 8.6 Hz, 1H), 3.83 (dd, J=14.8, 4.9 Hz, 1H), 2.77 (s, 3H), 1.59 (d, J=6.8 Hz, 3H); MS (ESI): m/z 331 (M+H).

Workup

  1. extractionextracted with EtOAc (50 mL)
  2. washThe organic phase was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed over silica gel using 100% CH2Cl2

Sources & evidence

ORD record
ord-ad2bc5fb650e41159de949603ccdbdad
Source dataset
uspto-grants-2015_02
Patent number
US08957104B2

Reaction notes

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