Acetic Acid → 6-(Trifluoromethyl)indole

HRID 1836644Notes

Reaction equation

HRID 1836644 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-f652b6e7537943beae9ffc212850953f
Source dataset
uspto-grants-2004_08
Patent number
US06777437B2

Reaction notes

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