Synthesis
General procedure for the synthesis of ethyl 3-methyl-1,2,4-oxadiazole-5-carboxylate from ethyl oxalyl chloride monoethyl ester and N'-hydroxyacetimidamide: At room temperature, (E)-N'-hydroxyacetimidamide (2.0 mmol, 1.0 g, 13.50 mmol, 1 equiv.) and pyridine (4.35 mL, 54.0 mmol, 4 equiv.) were dissolved in anhydrous dichloromethane ( 40 mL) and acetyl chloride (2.4 g, 18.0 mmol, 1.3 equiv) was added slowly. The reaction mixture was stirred under reflux conditions for 14 hours. After completion of the reaction, it was cooled to room temperature and the reaction was quenched with saturated ammonium chloride solution (30 mL). The aqueous phase was extracted with dichloromethane (2 x 50 mL). The organic phases were combined, washed with saturated sodium bicarbonate solution (50 mL), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford ethyl 3-methyl-1,2,4-oxadiazole-5-carboxylate (2.2 mmol, 1.32 g, 8.45 mmol, 63% yield) as a yellow oil, which was used directly in the next step of the reaction.LCMS analysis showed a purity of 92%, retention time was 2.0 min, (M + H)+: 157.
