反应详情

A suspension of 1.0 g (0.0027 mole) of ethyl 6,7-difluoro-1-(4-fluorophenyl)-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate (XXXII, R11 =4-fluorophenyl) (prepared as described in Preparation 4) in 15 ml of 42% aqueous hydrofluoroboric acid was stirred at 90°-100° C. for 3 hours, after which it was poured into water. The precipitated crystals were collected by filtration to give 1 g of a chelate (IV) as a colorless powder. The whole of this was dissolved in 3 ml of dimethyl sulfoxide, and the solution was mixed with 0.43 g (0.005 mole) of anhydrous piperazine. The mixture was then stirred at 60°-70° C. for 3 hours. At the end of this time, the reaction mixture was allowed to cool to room temperature. On adding water, a chelate (V) separated out as yellow crystals, which were collected by filtration. The crystals were dissolved in a mixture of 150 ml of 80% aqueous methanol and 5 ml of triethylamine, and the solution was heated under reflux for 4 hours. It was then allowed to cool to room temperature, and insoluble materials were removed by filtration. The filtrate was then concentrated by evaporation under reduced pressure to give crystals. These were washed with ethanol to give 0.73 g of 6-fluoro-1-(4-fluorophenyl)-8-methoxy-7-(1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid as a colorless powder.

1. filtrationThe precipitated crystals were collected by filtration