反应详情

A 360 mg (1.00 mmol) portion of (R)-1-benzyloxycarbonyl-3-(1-tert-butoxycarbonylaminomethylcyclopropyl)pyrrolidine was dissolved in 10 ml of methanol to which was subsequently added 125 mg of 5% (v/v) palladium-carbon to carry out 3.5 hours of stirring at room temperature in a stream of hydrogen. After filtration through celite, methanol was evaporated. The resulting residue was mixed with 1 ml of triethylamine and 159 mg (0.50 mmol) of 6,7,8-trifluoro-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-5-hydroxy-4-oxoquinoline-3-carboxylic acid which has been dissolved in 10 ml of acetonitrile, and the thus prepared mixture was heated under reflux for 1 hour. After completion of the reaction, the reaction solution was mixed with 10% citric acid and extracted with chloroform (50 ml×3). The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated. A 5 ml portion of concentrated hydrochloric acid was added dropwise to the resulting residue, followed by 1.5 hours of stirring at room temperature. After completion of the reaction, the reaction solution was adjusted to pH 12 with sodium hydroxide aqueous solution and then to pH 7.4 with hydrochloric acid, and the thus precipitated crystals were collected by filtration. The resulting filtrate was extracted with chloroform (100 ml×3). The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated. Thereafter, the resulting residue and the collected crystals were combined, and recrystallized from ethanol-liquid ammonia to yield 227 mg (82%) of the title compound.

1. filtrationAfter filtration through celite, methanol
2. customwas evaporated
3. temperaturethe thus prepared mixture was heated
4. temperatureunder reflux for 1 hour
5. customAfter completion of the reaction
6. extractionextracted with chloroform (50 ml×3)
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. customthe solvent was evaporated
9. additionA 5 ml portion of concentrated hydrochloric acid was added dropwise to the resulting residue
10. waitfollowed by 1.5 hours
11. customAfter completion of the reaction
12. filtrationto pH 7.4 with hydrochloric acid, and the thus precipitated crystals were collected by filtration
13. extractionThe resulting filtrate was extracted with chloroform (100 ml×3)
14. dry with materialThe organic layer was dried over anhydrous sodium sulfate
15. customthe solvent was evaporated
16. customrecrystallized from ethanol-liquid ammonia