General procedure for the synthesis of 5-bromo-1,4-dimethyl-1H-imidazole from 4-methyl-5-bromoimidazole and iodomethane: Sodium hydride (60% wt/wt, dispersed in mineral oil, 149 mg, 3.73 mmol, 1.2 eq.) was suspended in anhydrous tetrahydrofuran (10 mL) under nitrogen protection and cooled to 0 °C. To this suspension a solution of 5-bromo-4-methyl-1H-imidazole (500 mg, 3.11 mmol) in tetrahydrofuran (5 mL) was added dropwise. The reaction mixture was stirred at room temperature for 30 min before methyl iodide (661 mg, 4.66 mmol, 1.5 equiv) was added. Stirring was continued for 30 min, after which the reaction mixture was partitioned between ethyl acetate (100 mL) and water (20 mL). The organic phase was separated, dried over magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and the resulting crude product was purified by silica gel column chromatography (40 g) using a gradient elution of dichloromethane with methanol (0:100 to 5:95) to afford the target compound 5-bromo-1,4-dimethyl-1H-imidazole as a colorless oil (80 mg, 15% yield).1H NMR (400 MHz, CDCl3): δ = 2.10 (s, 3H) , 3.59 (s, 3H), 7.53 (s, 1H). MS: APCI+ m/z = 174, 176 [MH+].
