4-Toluenesulfonyl chloride → 3-Ethyl-2-methoxy-6-methyl-5-[1,3,4]oxadiazol-2-yl-pyridine

Participants

Reaction Conditions

Reaction Steps

Into a microwave vial is added 5-ethyl-6-methoxy-2-methyl-nicotinic acid N′-formylhydrazide (132 mg), tosyl chloride (64 mg, 0.336 mmol), and 2-t-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine on polystyrene (2.2 mmol/g, 634 mg, 1.39 mmol) and anhydrous tetrahydrofuran (6 mL). The vial is flushed with nitrogen, sealed and heated in the CEM Discover microwave at 145° C. holding at that temperature for 3 min, with a maximum pressure of 6 bar. The reaction is evaporated and the residue is directly purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane. Fractions containing the product are combined and the solvent evaporated, and further purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane. Fractions containing the product are combined, evaporated and re-purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (1:0 increasing to 99:1). Fractions containing the product are combined, evaporated and re-purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:ethyl acetate (6:1). Fractions containing the product are combined and the solvent evaporated. The clean fraction containing the product is evaporated to give 3-ethyl-2-methoxy-6-methyl-5-[1,3,4]oxadiazol-2-yl-pyridine (10 mg, 8% yield). MS: m/e=220 (M+H); 1H NMR (CDCl3, δ, ppm): 8.45 (1H, d), 7.91 (1H, s), 4.01 (3H, s), 2.81 (3H, s), 2.61 (2H, q), 1.13 (3H, t).

Provenance & Evidence