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 racemic DFTQ with 2,3-di-O-benzoyl-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.