Nuclear hydroxylated metabolite of fluradoline (2-fluoro-11-[(β-methylamino)ethylthio]dibenz[b,f]oxepin hydrochloride). Identification and synthesis

Fluradoline (2-fluoro-11-[β-(methylamino)ethylthio]dibenz[b,f]oxepin), a novel analgesic with an unique profile, was found to be extensively metabolized in man as well as in other species. One of the major metabolites of this drug appeared to be a nuclear hydroxylated derivative of the parent compound, and the site of enzymatic hydroxylation was established to be C(7) by using high-field proton nuclear magnetic spectroscopy. This structural assignment was subsequently confirmed by the synthesis of an authentic sample of 2-fluoro-7-hydroxy-11-[β-(methylamino)ethylthio]dibenz[b,f]oxepin (2a).