An efficient and regioselective synthesis of 4- and 7-alkoxyindoles has been developed from commercially available starting materials such as 3-halophenols and 3-chloroanisole. Directed ortho-metalation followed by two palladium-catalyzed processes, a Sonogashira coupling and a tandem amination/cyclization reaction, allows the synthesis of regiochemically pure 4- and 7-substituted indoles. This strategy has been successfully applied to the preparation of 2-[3-(2-amino-2-oxoacetyl)-1-benzyl-2-ethyl-1H-indol-4-yloxy]acetic acid (LY315920), a known inhibitor of phospholipase A2.
