Process Development of Halaven®: Synthesis of the C14-C35 Fragment via Iterative Nozaki-Hiyama-Kishi Reaction-Williamson Ether Cyclization

Multikilogram manufacturing process of the Halaven (R) C14-C35 fragment is described. The synthesis features convergent assembly of subunits by iterative asymmetric Ni/Cr-mediated coupling executed in fixed equipment.