Practical Synthesis of Reactive Immuno-PET Linker-Chelator (1R,2R)-RESCA-TFP

We herein report the evolution of decagram syntheses of a single enantiomer of immuno-PET linker-chelator (1R,2R)-RESCA-TFP (1) from commercially available (1R,2R)-1,2-diaminocyclohexane. The syntheses feature a reductive amination, a trialkylation, a saponification followed by EDCI-promoted TFP ester formation, and finally a t-Bu ester global deprotection. While the first-generation synthesis required chromatographic purification of process intermediates and 1, the second-generation synthesis implemented salt formation and direct isolation by filtration, thus eliminating all preparative purification operations.