Potassium Carbonate → 2-methyl-4-(trifluoromethyl)-1H-indole

HRID 913489Notes

Reaction equation

HRID 913489 reaction equation
[CH3:1][C:2]1[N:3](S(C2C=CC=CC=2)(=O)=O)[C:4]2[C:9]([CH:10]=1)=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:7]=[CH:6][CH:5]=2.C([O-])([O-])=O.[K+].[K+]>CO.O>[CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[C:8]([C:11]([F:13])([F:12])[F:14])[CH:7]=[CH:6][CH:5]=2

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 578003011-benzenesulfonyl-2-methyl-4-trifluoromethyl-1H-indole

Product 1

HCID 196970222-methyl-4-(trifluoromethyl)-1H-indoleYield 138.7%

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

A mixture of 2-methyl-1-(phenylsulfonyl)-4-(trifluoromethyl)-1H-indole (13.5 g, 39.82 mmol; step C above) and K2CO3 (27.5 g) in MeOH/H2O (2:1, 300 mL) was heated at reflux temperature. After 14 h the mixture was cooled and concentrated in vacuo. The residue was partitioned between Et2O/H2O, the layers were separated and the aqueous layer was extracted with Et2O (×2). Combined organics were washed (H2O, brine), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via column chromatography (SiO2, 1:1 EtOAc/hexanes eluent), affording 11.0 g of the deprotected indole as a yellow oil: 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J=8.0 Hz, 1H), 7.35 (d, J=8.0 Hz, 1H), 7.15 (t, J=8.0 Hz, 1H), 6.46 (s, 1H), 2.48 (s, 3H); MS (ES) m/z 200 (M+1).

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature
  3. temperatureAfter 14 h the mixture was cooled
  4. concentrationconcentrated in vacuo
  5. customThe residue was partitioned between Et2O/H2O
  6. customthe layers were separated
  7. extractionthe aqueous layer was extracted with Et2O (×2)
  8. washCombined organics were washed (H2O, brine)
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customThe residue was purified via column chromatography (SiO2, 1:1 EtOAc/hexanes eluent)

Sources & evidence

ORD record
ord-12265aae12294fcfb5994232fefd30fc
Source dataset
uspto-grants-2011_09
Patent number
US08026262B2

Reaction notes

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