Synthesis of carbon-14-labeled isotopomer of 6-(4-methanesulfonylphenyl)-5-[4-(2-piperidin-1-yl-ethoxy)phenoxy]-naphthalen-2-ol HCL salt (LY2066948-[14C] HCL salt)

Carbon‐14‐labeled 6‐(4‐methanesulfonylphenyl)‐5‐[4‐(2‐piperidin‐1‐yl‐ethoxy)phenoxy]naphthalen‐2‐ol, a novel selective estrogen receptor modulator (SERM) was synthesized. The key component, 6‐methoxy‐1‐tetralone‐[carbonyl‐14C], was synthesized from 3‐(3‐methoxyphenyl)‐propionic acid via an intra‐molecular Friedel–Crafts acylation of 4‐(3‐methoxyphenyl)butanoic acid‐[carboxy‐14C]. A palladium catalyzed alpha‐keto arylation of 6‐methoxy‐1‐tetralone with 4‐methanesulfonyl‐phenyl bromide, followed by a sequence of bromination, DDQ dehydrogenation, aryl Ullmann reaction, and demethylation with BBr3 gave the desired product LY2066948‐[14C]. Copyright © 2007 John Wiley & Sons, Ltd. Synthesis of carbon‐14‐labeled isotopomer of 6‐(4‐methanesulfonyl‐phenyl)‐5‐[4‐(2‐pip eridin‐1‐yl‐ethoxy)phenoxy]‐naphthalen‐2‐ol HCl salt (LY2066948‐[14C]) HCl salt. Copyright © 2007 John Wiley & Sons, Ltd.