Ethyl 4-methyl-1H-imidazole-5-carboxylate (463 mg, 3.00 mmol, 1 eq.) and iodomethane (0.19 mL, 3.00 mmol, 1 eq.) were added to potassium carbonate (828 mg, 6.00 mmol, 2 eq.) in acetonitrile. The mixture was heated to reflux and stirred overnight. After completion of the reaction, it was cooled to room temperature, filtered to remove inorganic salts and the filtrate was concentrated to dryness. The crude product was purified by silica gel column chromatography (80 g silica gel) with an elution gradient of 100% EtOAc to 10% CH3OH/DCM to isolate the two regional isomers. The first eluted isomer was identified as ethyl 1,4-dimethyl-1H-imidazole-5-carboxylate (185 mg, 1.95 mmol, 35% yield) by NOESY and HMBC NMR analysis. Its 1H NMR (400 MHz, DMSO-d6) data were as follows: δ 7.74 (s, 1H), 4.25 (q, J = 7.14 Hz, 2H), 3.76 (s, 3H), 2.34 (s, 3H), and 1.30 (t, J = 7.10 Hz, 3H).LC-MS (ES+) showed the molecular ion peak m/z 169.08 [M + H]+.
