Hydrochloric Acid → HCID 19072265, compound

Participants

Reaction Steps

30.7 g of sodium hydride was suspended in 1.8 1 of N,N-dimethylformamide and 261 g of di-t-butyl malonate was dropped thereinto over 2 hours under ice-cooling. After the completion of the addition, 100 g of ethyl 1-cyclo-propyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolone-carboxylate was added thereto. Then the mixture was stirred successively at 50° to 60° C. for 3 hours, at room temperature for 12.5 hours, at 50° to 60° C. for 11 hours and at room temperature for 14 hours. Next, conc. hydrochloric acid was added thereto under ice-cooling to thereby regulate the pH value of the mixture to 1. After adding ethyl acetate and water, the organic layer was collected, successively washed with water and a saturated aqueous solution of sodium hydro-gencarbonate and dried over anhydrous sodium sulfate. After removing the solvent under reduced pressure, diisopropyl ether was added to the obtained residue and the solid thus precipitated was collected by filtration. To the solid thus obtained, 500 ml of methylene chloride and 500 ml of tri-fluoroacetic acid were added. Then the mixture was stirred at room temperature for 66 hours. After removing the solvent under reduced pressure, diethyl ether was added to the obtained residue and the solid thus precipitated was collected by filtration. The solid thus obtained was suspended in 700 ml of methylene chloride and 300 ml of methanol. Then a diphenyldiazomethane-dichloromethane solution was dropped thereinto until the color of the mixture did not fade any more. Then the excessive diphenyldiazomethane was decomposed with acetic acid and the solvent was removed under reduced pressure. To the obtained residue, diethyl ether was added. The solid thus precipitated was collected by filtration. Thus 96.7 g of ethyl 1-cyclopropyl-7-diphenylmethoxycarbonylmethyl-6-fluoro-8-methoxy-1,4-dihydro-4-oxo-3-quinolinecarboxylate was obtained (yield: 59.0%).

Provenance & Evidence