Methyl iodide → 1,4,6-Trimethyl-1H-indole

Reaction equation

[CH3:1][C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].I[CH3:15]>CN(C=O)C>[CH3:15][N:6]1[C:7]2[C:3](=[C:2]([CH3:1])[CH:10]=[C:9]([CH3:11])[CH:8]=2)[CH:4]=[CH:5]1

Participants

Procedure

A solution of the 4,6-dimethylindole (750 mg, 5.2 mmol) in DMF (20 mL) is cooled to 0° C. under nitrogen and is treated with 60% sodium hydride in mineral oil (413 mg, 10.3 mmol). After stirring for 15 minutes the iodomethane (0.4 mL, 6.2 mmol) is introduced and the cooling bath is removed. After 30 minutes the solution is quenched with water (5 ml) and then concentrates to reduce the volume of DMF. The reaction is poured into a mixture of water (200 mL) and EtOAc (100 mL). The layers are separated and the aqueous phase is extracted with EtOAc (3×200 mL). The combined organics are washed with water (3×), dried (MgSO4), filtered and concentrated. The residue is purified by flash chromatography with 10% EtOAc in Hexane as the eluent to afford 1,4,6-Trimethyl-1H-indole (700 mg, 80%) as a white solid.