Synthesis of Selective Estrogen Receptor Degrader GDC-0810 via Stereocontrolled Assembly of a Tetrasubstituted All-Carbon Olefin

We report an efficient synthesis of GDC-0810 on the basis of a sequence involving a highly stereoselective lithium tert-butoxide-mediated enolization tosylation (>= 95:5 E:Z) and a Pd-catalyzed Suzuki Miyaura cross-coupling as key steps. Global deprotection, pyrrolidine salt formation, and final active pharmaceutical ingredient (API) form control/isolation produced GDC-0810 free acid in a 40% overall yield with >99.0% purity as ascertained by HPLC analysis.