An advantageous route to oxcarbazepine (trileptal) based on palladium-catalyzed arylations free of transmetallating agents.
[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.
Carril
Mónica
M
Kimika Organikoa II Saila, Zientzia eta Teknologia Fakultatea, Euskal Herriko Unibertsitatea, Bilbao, Spain.
SanMartin
Raul
R
Churruca
Fátima
F
Tellitu
Imanol
I
Domínguez
Esther
E
D000098:Acetophenones / Q000737:chemistry*; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry; D001969:Bromobenzenes / Q000737:chemistry*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D007659:Ketones / Q000737:chemistry; D015394:Molecular Structure; D000078330:Oxcarbazepine; D010165:Palladium / Q000737:chemistry*; D013997:Time Factors; D014867:Water / Q000737:chemistry
D000098:Acetophenones; D000927:Anticonvulsants; D001969:Bromobenzenes; D007659:Ketones; D014867:Water; D002220:Carbamazepine; C055495:2-aminoacetophenone; C102879:1,2-dibromobenzene; D010165:Palladium; D000078330:Oxcarbazepine