Methanol → 2-methyl-1-(1-(methylsulfonyl)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile

HRID 1851106Notes

Reaction equation

HRID 1851106 reaction equation
[CH3:1][C:2]1[N:3]([CH:17]([CH3:21])[CH2:18]SC)[C:4]2[C:9]([CH:10]=1)=[C:8]([C:11]([F:14])([F:13])[F:12])[C:7]([C:15]#[N:16])=[CH:6][CH:5]=2.O[O:23][S:24]([O-:26])=O.[K+].[CH3:28]O>O>[CH3:1][C:2]1[N:3]([CH:17]([CH3:21])[CH2:18][S:24]([CH3:28])(=[O:26])=[O:23])[C:4]2[C:9]([CH:10]=1)=[C:8]([C:11]([F:13])([F:12])[F:14])[C:7]([C:15]#[N:16])=[CH:6][CH:5]=2

Participants

5

Reactant 3

HCID 887MethanolHCID 23707502Potassium hydroxy sulfite2×HCID 867091622-methyl-1-(1-(methylthio)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Product 1

HCID 867091632-methyl-1-(1-(methylsulfonyl)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To an ice-cold solution of 2-methyl-1-(1-(methylthio)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile (Example 8) (0.045 g, 0.144 mmol) in MeOH (4 mL) was added a solution of Oxone (0.133 g, 0.216 mmol) in water (2 mL). After 1 h, additional Oxone (0.100 g, 0.163 mmol) was added, and the mixture was stirred at rt. After 30 min, the reaction mixture was diluted with water (10 mL) and extracted with EtOAc (20 mL). The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by preparative HPLC (Phenomenex Luna column; gradient: 10-100% MeCN-water with 0.1% TFA). The fractions with product were basified with aq. saturated K2CO3 solution, and then concentrated down to the aqueous phase, which was extracted with EtOAc. The organic phase was washed with brine, dried over Na2SO4, filtered and concentrated to give 2-methyl-1-(1-(methylsulfonyl)propan-2-yl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile: MS (ESI): m/z 345 (MH+).

Workup

  1. waitAfter 30 min
  2. extractionextracted with EtOAc (20 mL)
  3. washThe organic phase was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by preparative HPLC (Phenomenex Luna column; gradient: 10-100% MeCN-water with 0.1% TFA)
  8. concentrationconcentrated down to the aqueous phase, which
  9. extractionwas extracted with EtOAc
  10. washThe organic phase was washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-7e427cf4950c4a539effe113aef0107c
Source dataset
uspto-grants-2015_02
Patent number
US08957104B2

Reaction notes

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