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

Mónica Carril, Raul SanMartin, Fátima Churruca, Imanol Tellitu, Esther Domínguez

Index: Org. Lett. 7(22) , 4787-9, (2005)

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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.