Acetic Acid → 6-(Trifluoromethyl)indole

HRID 2416268Notes

Reaction equation

HRID 2416268 reaction equation
[N+]([C:4]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:5]=1[CH2:14][C:15]#[N:16])([O-])=O.O.C(O)(=O)C>CCO.[Pd]>[F:13][C:10]([F:11])([F:12])[C:8]1[CH:9]=[C:4]2[C:5]([CH:14]=[CH:15][NH:16]2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 962WaterHCID 2775792[2-Nitro-4-(trifluoromethyl)phenyl]acetonitrile

Product 1

HCID 27775236-(Trifluoromethyl)indoleYield 114.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

The commercially available (2-nitro-4-trifluoromethylphenyl) acetonitrile (14.0 g, 60.8 mmol) was dissolved in 9:1 EtOH:H2O (50 mL) and glacial acetic acid (1.4 mL). This mixture was hydrogenated over 10% Pd/C (5.0 g) at 50 psi for 16 h at room temperature. The reaction was filtered over celite and evaporated in vacuo. The residue was partitioned between saturated aqueous sodium carbonate and dichloromethane (2×200 mL) and the combined organic extract was dried over sodium sulfate, filtered, and concentrated in vacuo. The crude material was purified by silica gel column chromatography (hexanes/ethyl acetate, 20:1, 9:1, 5:1) to afford 12.9 g (65% yield) of 6-trifluoromethyl-1H-indole as a yellow solid: 1H NMR (400 MHz, CDCl3) 8.36, (1H, br s), 7.72 (2H, m), 7.37 (2H, m), 6.63 (1H, m); MS m/e 184 (M−H)−. Anal calcd. for C9H6F3N: C, 58.38; H, 3.26; N, 7.56. Found: C, 58.30; H, 2.92; N, 7.49.

Workup

  1. filtrationThe reaction was filtered over celite
  2. customevaporated in vacuo
  3. customThe residue was partitioned between saturated aqueous sodium carbonate and dichloromethane (2×200 mL)
  4. extractionthe combined organic extract
  5. dry with materialwas dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude material was purified by silica gel column chromatography (hexanes/ethyl acetate, 20:1, 9:1, 5:1)

Sources & evidence

ORD record
ord-a3ad3c8badec459a8785c4a145eae2e5
Source dataset
uspto-grants-2004_11
Patent number
US06822100B2

Reaction notes

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