Synthesis of 14 C‐labeled 4‐hydroxyindole as an intermediate for the preparation of ( S )‐2‐[4‐[2‐[3‐(indol‐2‐[ 14 C]‐4‐yloxy)‐2‐hydroxypropylamino]‐2‐methylpropyl]‐phenoxy]pyridine‐5‐carboxamide (LY368842‐[indole‐ 14 C]) glycolate

Synthesis of 4‐hydroxyindole labeled with 14 C at the 2‐position was accomplished based on the vicarious nucleophilic substitution reaction of benzyl‐protected 3‐nitrophenol with p ‐chlorophenoxyacetonitrile‐[1‐ 14 C]. This was followed by the reductive cyclization of o ‐nitrocyanomethyl derivative by palladium catalyzed hydrogenation. p ‐Chlorophenoxyacetonitrile‐[1‐ 14 C] was prepared from commercially available p ‐chlorophenoxymethyl chloride and sodium cyanide‐[ 14 C]. 4‐Hydroxyindole‐[2‐ 14 C] was used for the synthesis of 14 C‐labeled β 3 adrenergic agonist LY368842. Copyright © 2002 John Wiley & Sons, Ltd.