Synthesis of Filibuvir. Part II. Second-Generation Synthesis of a 6,6-Disubstituted 2H-Pyranone via Dieckmann Cyclization of a β-Acetoxy Ester

This paper describes an improved sequence for the conversion of an oxazolidinone (3) to a β-keto lactone (5). The primary drivers behind this change were the modest and variable yields observed in the intramolecular cyclization to generate the β-keto lactone. Changing the cyclization substrate from oxazolidinone to alkyl ester offered a significantly improved cyclization, as well as improvements in the alkyne hydrogenation. Selection of the optimal substrates for methanolysis and intermediate salt formation are also described.