Stereochemical Editing via Coupled Epimerization and Optical Resolution to Sustainably Manufacture a Key Adagrasib Building Block

Adagrasib’s Second-Generation Synthesis: Transitioning from Route Scouting to Optimization

“…Stirring in methanol was already part of the debenzylation process (Figure ), and simply increasing the volume of the methanol charge allowed this operation to also serve the function of effectively triturating the dihydrochloride salt. Combined with other innovations, this led to a more than doubling of the yield from 34 to 74% over the course of two bond-forming operations.…”