Methyl iodide → 1,4-Dimethylindole

Reaction equation

[CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].I[CH3:14]>C1COCC1>[CH3:14][N:6]1[C:7]2[C:3](=[C:2]([CH3:1])[CH:10]=[CH:9][CH:8]=2)[CH:4]=[CH:5]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 4-methyl-1H-indole (CAS#16096-32-5, 2.82 mL, 22.9 mmol) in THF (100 mL) at 0° C. was added sodium hydride (60% dispersion in oil, 1.37 g, 34.3 mmol). The reaction was permitted to stir for 16 minutes at 0° C. and was then warmed to room temperature for 60 minutes. The reaction mixture was then re-cooled to 0° C. and iodomethane (1.86 mL, 29.7 mmol) was added. The reaction was then put at room temperature and permitted to stir for 45 minutes. The reaction was then quenched with saturated aqueous ammonium chloride and concentrated to approximately half of its original volume. The mixture was then diluted with water and dichloromethane and the layers were separated. The aqueous layer was then extracted two additional times with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane 0 to 30%) to afford 1,4-dimethyl-1H-indole; 1H NMR (400 MHz, CDCl3) δ ppm 2.57 (s, 3H), 3.80 (s 3H), 6.51 (d, J=3.0 Hz, 1H), 6.93 (d, J=6.7 Hz, 1H), 7.06 (d, J=3.0 Hz, 1H), 7.13-7.21 (m, 2H).