A Scalable Synthesis of an Azabicyclooctanyl Derivative, a Novel DPP-4 Inhibitor

A practical synthetic strategy to a chiral azabicycclooctanyl derivative (1), a potent DPP-4 inhibitor, starting from a commercially available nortropine is described. The stereogenic center of 1 was established employing a modified protocol of Ellman’s diastereoselective addition of a benzylic nucleophile to tert-butanesulfinimine. Other key steps include Corey−Chaykovsky reaction, Meinwald rearrangement, and CDMT-promoted amide bond formation involving a sterically hindered amine 2.