Abstract: In this paper, polysubstituted indolizine derivative 3 was synthesized with ethyl pyridine acetate 1 and benzyl bromide 2 as raw materials, triethyl orthoformate as additive and Cs₂CO₃ as base in acetonitrile solution by reflux reaction for 7 h. The yield was medium to excellent. It was also found that triethyl orthoformate had water absorption in the reaction system. The synthesized products were characterized by ¹H NMR, ¹³C NMR and HRMS. The method described in the paper highlights the advantages of easily accessible raw materials, simple reaction procedure, and a straightforward synthesis route. This method offers a new approach for the synthesis of potential bioactive indolizine derivatives, which could be useful in the discovery of new drug candidates or bioactive compounds.