Abstract: A series of synthesis of some substituted isoxazole derivatives using efficient ultra sound sonication method in methanol solvent. Firstly the synthesis of different substituted chalcones using substituted aldehydes and substituted acetophenones using triethylamine as base in ethanol solvent under sonication. In second step synthesized substituted chalcones is reacted with two equivalents of hydrochloride salt of ammonium hydroxide, sodium oxalate and methanol under sonication at 30-35OC to afford a substituted isoxazole derivatives in 90-98% of yields. The structures of the synthesized compounds were confirmed on the basis of NMR, and MS analysis. This method has a several advantages over current reaction methodologies, such as shorter reaction times, simple work-up procedure and good percent yields.