A convenient one-pot synthesis of 1,2,4-oxadiazoles is described. The condensation of carboxylic acids and amidoximes in the presence of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and N-methylmorpholine (NMM) has been employed to synthesize a variety of 3,5-disubstituted 1,2,4-oxadiazoles in good to excellent yields. The methodology has been applied for the synthesis of a metabotropic glutamate subtype 5 (mGlu5) receptor antagonist.