108115-66-8Relevant articles and documents
Synthesis of [1-15N,2-13C]-labeled difloxacin
Schmidt, Burkhard,Schumacher-Buffel, Ramona,Thiede, Brigitte,Schaeffer, Andreas
experimental part, p. 1221 - 1227 (2011/10/02)
The synthesis of [1-15N,2-13C]-difloxacin, an arylfluoroquinolone antibacterial agent, is reported. As a crucial initial step, the starting materials ethyl 2,4,5-trifluorobenzoylacetate, [formyl- 13C]-triethyl orthoformate, and [15N]-4-fluoroaniline were reacted to ethyl [15N,3-13C]-3-(4-fluoroanilino)-2-(2,4, 5-trifluorobenzoyl)acrylate. After cyclization and ester cleavage, the resulting intermediate was reacted with 1-methylpiperazine to [1-15N,2- 13C]-1-(4-fluorophenyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1, 4-dihydro-4-oxoquinoline-3-carboxylate, i.e., [1-15N,2- 13C]-difloxacin. The overall yield was 62% based on the non-labeled and 43% based on the labeled starting materials (both used in 1.4 molar excess). The product was identified by 1H-, 13C-, and 15N-NMR spectroscopy and by cochromatography (TLC, HPLC) with an authentic reference; its purity (HPLC) was above 98%. Prior to synthesis of [1-15N,2-13C]-difloxacin, non-labeled difloxacin was synthesized in order to optimize procedures and to identify and characterize all intermediates.