Quinoline → 4-Methyl-1h-indole-5-carbonitrile

HRID 2181196Notes

Reaction equation

HRID 2181196 reaction equation
Br[C:2]1[C:3]([CH3:14])=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](C(O)=O)=[CH:5]2.[N:15]1C2C(=CC=CC=2)C=C[CH:16]=1>>[CH3:14][C:3]1[C:2]([C:16]#[N:15])=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[CH:6][NH:7]2

Participants

3

Reactant 2

HCID 7047QuinolineHCID 224856945-bromo-4-methyl-1H-indole-2-carboxylic acid

Product 1

HCID 224856884-Methyl-1h-indole-5-carbonitrile

Conditions

Temperature
230 °C

Procedure

4.71 g (18.5 mmol) of 5-bromo-4-methyl-1H-indole-2-carboxylic acid and 5.03 g (56.2 mmol) of cuprous cyanide were dissolved in 35 ml of quinoline and the solution heated at 230° C. for 90 minutes. The reaction mixture was then cooled down to ambient temperature and poured onto crashed ice. The pH was adjusted to pH 2-3 and the mixture subsequently extracted 3 times with ether. The combined organic phases were washed with water, dried over magnesium sulfate and evaporated to give a crude product which was purified by chromatography (silicagel, eluent: gradient of n-heptane/ethyl acetate) to yield 2.36 g of 4-methyl-1H-indole-5-carbonitrile as light brown solid.

Workup

  1. temperatureThe reaction mixture was then cooled down to ambient temperature
  2. additionpoured
  3. extractionthe mixture subsequently extracted 3 times with ether
  4. washThe combined organic phases were washed with water
  5. dry with materialdried over magnesium sulfate
  6. customevaporated
  7. customto give a crude product which
  8. customwas purified by chromatography (silicagel, eluent: gradient of n-heptane/ethyl acetate)

Sources & evidence

ORD record
ord-77a277b810434e9cab326ecf74d9d7c7
Source dataset
uspto-grants-2005_05
Patent number
US06890947B2

Reaction notes

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