An advantageous route to oxcarbazepine (trileptal) based on palladium-catalyzed arylations free of transmetallating agents

Org Lett. 2005 Oct 27;7(22):4787-9. doi: 10.1021/ol051291p.

Abstract

[reaction: see text] A new route to oxcarbazepine (Trileptal), the most widely prescribed antiepileptic drug, starting from commercially available 2'-aminoacetophenone and 1,2-dibromobenzene, is reported. The sequentially accomplished key steps are palladium-catalyzed intermolecular alpha-arylation of ketone enolates and intramolecular N-arylation reactions. After several experiments to establish the best conditions for both arylation processes, the target oxcarbazepine is obtained in a satisfactory overall yield, minimizing the number of steps and employing scalable catalytic procedures developed in partially aqueous media.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / chemistry*
  • Anticonvulsants / chemical synthesis
  • Anticonvulsants / chemistry
  • Bromobenzenes / chemistry*
  • Carbamazepine / analogs & derivatives*
  • Carbamazepine / chemical synthesis
  • Carbamazepine / chemistry
  • Catalysis
  • Ketones / chemistry
  • Molecular Structure
  • Oxcarbazepine
  • Palladium / chemistry*
  • Time Factors
  • Water / chemistry

Substances

  • Acetophenones
  • Anticonvulsants
  • Bromobenzenes
  • Ketones
  • Water
  • Carbamazepine
  • 2-aminoacetophenone
  • 1,2-dibromobenzene
  • Palladium
  • Oxcarbazepine