108: Development of a 3-step telescoped Cu-mediated hydroxylation, debenzoylation, and crystallization for the commercial route of Osivelotor

Abstract: The end-game development of the commercial route toward the hemoglobin modulator Osivelotor is described. The application of a synchronous late-stage Cu-mediated hydroxylation and debenzoylation provided the crude-active pharmaceutical ingredient, which upon subsequent crystallization in the presence of acid generated the API as an HCl salt in a 3-step telescoped sequence. Initial scale-up of this route was accomplished at 11.5 kg, followed by an 80 kg production batch in early 2025. This process demonstrates a more sustainable and economical alternative to traditional precious metal catalysis.