Imidazole → 3-Ethyl-5-imidazol-1-yl-2-methoxy-6-methyl-pyridine

Participants

Reaction Conditions

Reaction Steps

Into each of 2 microwave vials is added 3-bromo-5-ethyl-6-methoxy-2-methylpyridine (200 mg, 0.869 mmol), potassium carbonate (180 mg, 1.30 mmol), copper iodide (16 mg, 0.084 mmol), sodium hydroxide (84 mg, 2.10 mmol) and imidazole (59 mg, 0.869 mmol). The vials are flushed with N2 before anhydrous dimethylformamide (5.5 mL) is added and then sealed. Each reaction is heated in the CEM Discover microwave at 185° C. for 1 hr. The 2 reactions are combined diluted with water and extracted with 3 portions of dichloromethane. The combined dichloromethane layers are washed with 2 portions of 1 M aqueous sodium hydroxide, dried over magnesium sulfate and evaporated to give a dark oil. The crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (1:1). Fractions containing the product are combined. The solvent evaporated, and the residue is further purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (3:1, increasing to 2:1). Clean fractions containing the product are combined and evaporated to give 3-ethyl-5-(imidazol-1-yl)-2-methoxy-6-methyl-pyridine (53 mg, 14% yield) as a yellow oil. MS: m/e=218 (M+H); 1H NMR (300 MHz, CDCl3, δ ppm): 7.54 (1H, s) 7.22 (1H, s), 7.21 (1H, s), 7.00 (1H, s), 3.98 (3H, s), 2.59 (2H, q), 2.25 (3H, s), 1.10 (3H, t).

Provenance & Evidence