Novel Baeyer–Villiger Oxidation of Nucleosides Applied to the Large-Scale Synthesis of MeMOP: A Key Amidite in the GalXC Platform

The Baeyer–Villiger reaction is an established oxidative process that is applied for structural and functional group modification. We have applied the Baeyer–Villiger process to prepare 4′-oxo nucleosides. The application of Baeyer–Villiger oxidation to prepare MeMOP, a complex amidite used in the reported GalXC platform, will be discussed. A large-scale process to prepare MeMOP with an improved economic and operational safety risk profile will be highlighted. This novel application of the Baeyer–Villiger reaction to nucleoside platforms was used to scale up the MeMOP phosphoramidite process, which supported multiple clinical trials enabling siRNA campaigns.