The synthetic methods were studied for 6-methoxy-7-ethoxy-4-chloroquinoline in details. The 2-methoxy-5-nitrophenol was used as the raw material and the title compound was obtained via the O-alkylation, reduction reaction, thermal cyclization, hydrolysis, decarboxylation and chloration. The overall yield was 24%. During the O-alkylation process, compared to the acetone, acetonitrile and DMF, the acetonitrile was proved to be the optimal solvent, which gave rise to the yield increased and the aftertreatment simplified. In addition, one-pot synthesis and without solvent method was bought into the high temperature cyclization process. The one-pot method can greatly simplify the operation and improve the yield. The solvent-free reaction can reduce consumption and pollution. This method can provide an experimental basis for its application with the advantages of simple operation and higher yield from convenient raw materials.