Abstract: Norfloxacin is one of the outstanding representatives of the third generation of quinolone antibiotics,and there are a good deal of methods for synthesizing it. Forming boride is the most useful method. Piperazine condensation of intermediate (1-ethyl-6-fluoride-7-chloro-1,4-dihydro-4-oxo-
quinoline-3-carboxylic acid-O3O4)-bis-(acetate-O)-boron is a crucial step in norfloxacin production. Optimizing the best conditions of piperazine condensation by orthogonal test. Reaction temperature, time, reactant mixture ratio and the amount of solvent were discussed. The best condition of piperazine condensation was investigated by L16(44) orthogonal design. At the temperature of 70℃, 6 hours, molar ratio of anhydrous piperazine : chelate complex = 4:1, dosage of solvents toluene : DMF = 50 : 20 by mass ratio are the best conditions.