2,3-Epoxypropyl neodecanoate (EPDA) is an important synthon of eco-friendly coatings, and its preparation methods and the relevant reaction mechanisms remain to be further studied. In this work, the two-step preparation method of EPDA is investigated. Under the optimized process conditions in the acidolysis reaction, 99% conversion of neodecanoic acid and 91-93% effective utilization rate of epichlorohydrin could be realized. In the following ring-closure reaction, the two-step alkali treatment was applied, and it can significantly reduce the treatment time and improve the yield of EPDA by 3-5%. Besides, the mechanism of the acidolysis reaction catalyzed by tetramethylammonium chloride is proposed. The two chemical reaction pathways are put forward to explain the formation of side product dichloropropanol. Two effective ways to control the side reactions are suggested, including the control of temperature in the range of 70-90 degrees C and reducing the concentration of inorganic chlorine in the reaction system.