5-Bromo-3-methyl-1H-indole → 3-Methyl-1H-indole-5-carbonitrile
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]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
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).