A Chiron Approach to the Practical and Scalable Synthesis of the β₃‐Adrenergic Receptor Agonist Vibegron

This is the authors' abstract. We don't add key points for this paper.

A practical and scalable synthesis of the β 3 ‐adrenergic receptor agonist Vibegron has been developed using a streamlined chiral‐pool approach from readily available 4‐nitro‐ D ‐phenylalanine and ( R )‐mandelic acid. The synthesis features a key acid‐catalyzed N ‐acyl iminium ion cyclization followed by a highly diastereoselective reduction, enabling efficient construction of the cis ‐2,5‐disubstituted pyrrolidine core. Final amidation with a commercially available pyrrolopyrimidine sodium salt furnished Vibegron in excellent overall yield.