trans-3-Isopropyl-4-(2-methylcyclohexyloxy)-6-phenethylpyridin-2(1H)-one, as reverse transcriptase (NNRTIs), exhibited significant potent activity not only against wild-type HIV-1 strains but also on mutant strains. For furthering study this compound, the original synthetic route should be shorten to improve the total yield. In this report, we designed an efficient synthetic strategy to obtain the target compound with higher yield.