5-Bromo-3-methyl-1H-indole → 3-Methyl-1H-indole-5-carbonitrile

HRID 475252Notes

Reaction equation

HRID 475252 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH3:11].[Cu][C:13]#[N:14]>CCOC(C)=O>[CH3:11][C:5]1[C:4]2[C:8](=[CH:9][CH:10]=[C:2]([C:13]#[N:14])[CH:3]=2)[NH:7][CH:6]=1

Participants

4

Reactant 2

HCID 2547075-Bromo-3-methyl-1H-indoleHCID 178418546HCID 178418546, compound

Product 1

HCID 574751293-Methyl-1H-indole-5-carbonitrileYield 81.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
200 °C

Procedure

A vessel was charged with 5-bromo-3-methyl-1H-indole (1.06 g, 5.05 mmol), copper (I) cyanide (542.83 mg, 6.0608 mmol), and degassed NMP (10 mL), sealed and heated to 200° C. with stirring for 5 h, then at 110° C. for 16 h. The cooled reaction was diluted with EtOAc and the organic layer was washed sequentially with water and brine, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by SiO2 chromatography eluting with an EtOAc/heptane gradient (0 to 100% EtOAc) to afford 640 mg (81.1%) of 3-methyl-1H-indole-5-carbonitrile (192): 1H NMR (400 MHz, CDCl3): δ 8.22 (br s, 1H), 7.91 (s, 1H), 7.42-7.35 (m, 2H), 7.07 (s, 1H), 2.32 (s, 3H).

Workup

  1. customdegassed NMP (10 mL)
  2. customsealed
  3. waitat 110° C. for 16 h
  4. customThe cooled reaction
  5. washthe organic layer was washed sequentially with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by SiO2 chromatography
  10. washeluting with an EtOAc/heptane gradient (0 to 100% EtOAc)

Sources & evidence

ORD record
ord-8676f9931d46425799deb37683a042cf
Source dataset
uspto-grants-2014_01
Patent number
US08637537B2

Reaction notes

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