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

We herein report the evolution of decagram synthesesof a singleenantiomer 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 saponificationfollowed by EDCI-promoted TFP ester formation, and finally a t-Bu ester global deprotection. While the first-generationsynthesis required chromatographic purification of process intermediatesand 1, the second-generation synthesis implemented saltformation and direct isolation by filtration, thus eliminating allpreparative purification operations.