4-Toluenesulfonyl chloride → 2(2-Pyridyl)-5-ME-1,3,4-oxadiazole

Participants

Reaction Conditions

Reaction Steps

Into each of two microwave vials is added 5-ethyl-6-methoxy-2-methyl-nicotinic acid N′-acetyl-hydrazide (100 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). Each 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 6.5 bar. LC/MS shows the reaction is complete. The product from both the vials are combined and evaporated, and the residue is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (49:1). 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:ethyl acetate (3:1). Fractions containing the product are combined again and evaporated to give 3-ethyl-2-methoxy-6-methyl-5-(5-methyl-[1,3,4]oxadiazol-2-yl-pyridine (95 mg, 73% yield, 2 steps). MS: m/e=234 (M+H); 1H NMR (CDCl3, δ, ppm): 7.86 (1H, s), 4.00 (3H, s), 2.79 (3H, s), 2.55-2.65 (5H, m), 1.21 (3H, t).

Provenance & Evidence