Triethylamine → 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbonitrile

HRID 644017Notes

Reaction equation

HRID 644017 reaction equation
FC(F)(F)C(OC(=O)C(F)(F)F)=O.[CH:14]1([CH2:20][N:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][C:28]=3[O:30][CH3:31])[C:23]([C:32]([NH2:34])=O)=[CH:22]2)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.C(N(CC)CC)C.O1CCOCC1>O>[CH:14]1([CH2:20][N:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][C:28]=3[O:30][CH3:31])[C:23]([C:32]#[N:34])=[CH:22]2)[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 312751,4-DioxaneHCID 686974651-cyclohexylmethyl-7-methoxy-1H-indole-3-carboxylic acid amide

Product 1

HCID 686987431-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbonitrileYield 64.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Trifluoroacetic anhydride (12.0 g, 57.1 mmol) was added dropwise to a mixture of 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carboxylic acid amide (4.1 g, 14.3 mmol), triethylamine (11.6 g, 115 mmol), and 1,4-dioxane (250 ml) under ice-water cooling. The resulting mixture was stirred at room temperature for 12 h. Water (30 ml) was added and the resulting mixture was concentrated in vacuo. Water (300 ml) was added to the obtained residue, and the mixture was extracted with dichloromethane (4×300 ml). The organic layers were combined, washed with 5% aqueous sodium hydrogen carbonate and brine, dried over magnesium sulfate, and concentrated in vacuo. The obtained residue was purified by column chromatography eluting with 10% (v/v) ethyl acetate in n-heptane to afford 1-(cyclohexyl)methyl-7-methoxy-1H-indole-3-carbonitrile as a crystalline solid (2.48 g).

Workup

  1. concentrationthe resulting mixture was concentrated in vacuo
  2. additionWater (300 ml) was added to the obtained residue
  3. extractionthe mixture was extracted with dichloromethane (4×300 ml)
  4. washwashed with 5% aqueous sodium hydrogen carbonate and brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe obtained residue was purified by column chromatography
  8. washeluting with 10% (v/v) ethyl acetate in n-heptane

Sources & evidence

ORD record
ord-ea83d42b1c294693b0f60c08f8f92599
Source dataset
uspto-grants-2010_04
Patent number
US07700634B2

Reaction notes

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