A new synthetic route to 7‐halo‐1‐cyclopropyl‐6‐fluoro‐1,4‐dihydro‐4‐oxoquinoline‐3‐carboxylic acid, an intermediate for the synthesis of quinolone antibacterial agents

Abstract

Abstract Starting from m ‐fluorotoluene, 7‐chloro‐6‐fluoro‐ and 6,7‐difluoro‐1‐cyclopropyl‐1,4‐dihydro‐4‐oxoquino‐line‐3‐carboxylic acids, 3 and 16 were synthesized. Compounds 3 and 16 are useful intermediates for the synthesis of a class of quinolone antibacterial agents. The synthetic route involves two processes; i) construction of the quinoline ring by an intramolecular cyclization accompanied by the elimination of a nitro group and ii) introduction of fluorine atom by replacement of a nitro group with potassium fluoride. 7‐(3‐Amino‐1‐pyrroli‐dinyl)‐1‐cyclopropyl‐6‐fluoro‐1,4‐dihydro‐4‐oxoquinoline‐3‐carboxylic acid (18) was prepared from 3 or 16. The antibacterial activity of 18 compares favorably with that of ciprofloxacin (2) .