Here we present a novel and cost-effective method for synthesizing biologically important α-ketoesters in a single-step reaction. This approach involves a sequential cascade process within a single reaction vessel facilitated by KOtBu. It promoted cleavage of sp2 C(O)-N bond of isatins and new N-sp2 C(O) bond formation with benzoyl chloride. To our knowledge, this is the first instance of constructing the α-ketoester scaffold alongside an amide group through a one-pot process. In comparison to existing literature methods, our protocol offers several advantages: readily available starting materials, mild reaction conditions, a concise synthetic pathway, high sustainability, and excellent tolerance towards various functional groups. Given these strengths, we anticipate widespread use of this method in the synthesis of related α-ketoester scaffolds.