Synthesis of a Chiral α-(Aminooxy)arylacetic Ester. II. A Route through a Chiral 2-Hydroxy-2-phenylacetic Acid Derivative

A simple and practical synthetic route has been developed for the synthesis of a chiral α-(aminooxy) ester (S)-16, which is a synthetic intermediate for a potent antipseudomonal cephalosporin antibiotic M-14659. In this synthetic route, the key intermediate is α-hydroxy acid (R)-7 (100%ee), which is prepared by an asymmetric reduction of α-keto ester with NaBH4-(R,R)-tartaric acid followed by a hydrolysis and an optical resolution using l-Leu–NHNH2. (S)-16 is obtained stereoselectively through 3 steps from (R)-7. HPLC analyses and NMR studies have proved that the (S)-16 thus prepared is completely optically pure.