Synthetic Application of Lithiation Reactions : A Convenient Synthesis of 3, 4-Dihydro-5-hydroxycarbostyril, 1, 2, 3, 4-Tetrahydro-5-hydroxy-2-oxo-1, 7-naphthyridine, and Methyl 3-Methoxypyridine-4-carboxylate

Abstract

3, 4-Dihydro-5-hydroxycarbostyril (3), a key intermediate for a clinically used β-receptor blocking agent (1), and its 7-aza analog (4) were prepared by an acid-catalyzed cyclization of the N-pivaloylamino-esters (17 and 19), which were obtained by using organolithiation of 3-methoxy-5-(pivaloylamino) pyridine and m-pivaloylanisidine, followed by Wittig and catalytic hydrogenation reactions. Some related pyridine derivatives (15 and 24) were also prepared.