The reaction of 6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (I) with 1-bromo-2-fluoroethane (II) by means of NaI in hot DMF gives 6,7,8-trifluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (III), which is then condensed with N-methylpiperazine (IV) in refluxing pyridine.
A new synthesis of fleroxacin, labeled with fluorine-18, has been described: The reaction of 6,7,8-trifluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (I) with 2-bromoethanol (II) gives 6,7,8-trifluoro-1-(2-hydroxyethyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (III), which is condensed with N-methylpiperazine (IV), yielding 6,8-difluoro-1-(2-hydroxyethyl)-7-(4-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (V). The reaction of (V) with methanesulfonyl chloride affords the corresponding mesylate (VI), which is treated with [18F]-KF in dichloromethane at 80 C to give 6,8-difluoro-1-(2-fluoroethyl)-7-(4-methylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid ethyl ester (VII). Finally, this compound is hydrolyzed with NaOH.