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 ® C14–C35 fragment is described. The synthesis features convergent assembly of subunits by iterative asymmetric Ni/Cr-mediated coupling executed in fixed equipment.