A Practical Synthesis of (S)-(-)-Nadifloxacin: Novel Acid-Catalyzed Racemization of Tetrahydroquinaldine Derivative

(S)-(-)-Nadifloxacin [(S)-(-)-9-fluoro-6, 7-dihydro-8-(4-hydroxy-1-piperidyl)-5-methyl-1-oxo-1H, 5H-benzo[i, j]quinolizine-2-carboxylic acid, (S)-(-)-OPC-7251], an antibacterial agent, was synthesized from (S)-(-)-5, 6-difluoro-2-methyl-1, 2, 3, 4-tetrahydroquinoline (DFTQ), which was prepared by the optical resolution of recemic DFTQ with 2, 3-di-O-benzoxyl-L-tartaric acid. Racemization of the undesired enantiomer [(R)-(+)-DFTQ] was studied in the presence of various acids and the best result was obtained in the case of methanesulfonic acid. The absolute configuration of (-)-nadifloxacin was determined as S by X-ray crystallographic analysis.