Synthesis of the carbon-14 labeled isotopomers of (R)N-methyl-3-[2-methylphenoxyl]-benzenepropanamine hydrochloride (atomoxetine hydrochloride, LY139603), and two of its metabolites

Carbon-14 labeled Straterra(TM) (Atomoxetine HCl, LY139603, (-)-N-methyl-3-(2-methylphenoxy)-benzenepropanamine hydrochloride), a potent inhibitor of the presynaptic norepinephrine transporter, and two of its major metabolites were synthesized. The key component, S-(+)-3-chloro-1-phenyl-1-propanol-[1-C-14] was synthesized by Stille coupling of benzoyl chloride-[carbonyl-C-14] with vinyl tri-n-butylstannane, followed by HCl addition to the vinyl ketone, and asymmetric reduction of the ketone by Corey's CBS reagent. Mitsunobu reaction of this S-(+)-3-chloro-1-phenyl-1-propanol-[1-C-14] with various phenol derivatives, followed by converting the chloride to amines, gave desired products. Copyright (C) 2004 John Wiley Sons, Ltd.