The 2,5-bis(2,2,2-trifluoroethoxy)benzoyl chloride was synthesized from commercial 2,5-bis(2,2,2-trifluoroethoxy)benzoic acid through acylating chlorination with dichlorosulfoxide. Then piperidin-2-ylmethanamine was used for amination to obtain flecainide hydrochloride. Different alcohol solvents were selected for neutralization and salification. Flecainide was complexed with acetic acid to form target flecainide acetate. The ratio of raw materials, reaction time, and solvent on the yield were investigated. The optimized reaction conditions are as following: 1) n(2,5-bis(2,2,2-trifluoroethoxy)benzoic acid) ∶n(piperidin-2-ylmethanamine) =1∶1.8, 2) following converting the starting acid into acyl chloride, the acyl chloride was reacted with piperidine in THF for 2 hours to obtain flecainide hydrochloride, 3) with ethanol as the solvent, the quantity of flecainide was obtained by neutralization with NaOH in 0.5 h, 4) isopropyl alcohol was used as the solvent, refluxing with acetic acid for 0.5 h, leading to the target product. After two recrystallization process, the total yield of the 4-step reaction was 39.2%, and the purity of the final product was higher than 99.7% by HPLC analysis.