Alternative Approach to the Large-Scale Synthesis of the Densely Functionalized Pyrrolidone BMT-415200

The development of a multi-kilogram-scale synthetic route to enantiomerically pure ((2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl)methyl methanesulfonate (BMT-415200) 1 is described in this work. In this sequence, a safe and robust process of nine linear steps with four isolations was implemented. The synthesis features highly diastereoselective hydrogenation of enones 12, diastereoselective reduction of ketone 13, and deoxyfluorination of the corresponding secondary alcohol 8 followed by C-H oxidation of 9 to lactam 10. The target compound 1 was prepared in 19% overall yield with >99% purity from commercially available di-tert-butyl (S)-4-oxopyrrolidine-1,2-dicarboxylate 7.