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‐l‐phenyl‐l‐propanol‐[1‐ 14 C] was synthesized by Stille coupling of benzoyl chloride‐[carbonyl‐ 14 C] 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‐l‐phenyl‐l‐propanol‐[1‐ 14 C] with various phenol derivatives, followed by converting the chloride to amines, gave desired products. Copyright © 2004 John Wiley & Sons, Ltd.