反应详情

A mixture of 100 mg of 6,7,8-trifluoro-1-[(1R,2S)-2-fluorocyclopropyl]-5-methyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, 120 mg of (S)-3-t-butoxycarbonylaminopyrrolidine, and 3 ml of anhydrous dimethyl sulfoxide was heated at 100° to 120° C. for 1 hour with stirring, and dimethyl sulfoxide was removed under reduced pressure. Water was added to the residue, and the precipitated yellow crystals were collected by filtration. Three milliliters of trifluoroacetic acid was stirred under ice-cooling, and the above-obtained yellow crystals were slowly added thereto, followed by stirring at room temperature for 30 minutes. The trifluoroacetic acid was removed under reduced pressure, and the residue was dissolved in a 1N sodium hydroxide aqueous solution (pH 12). The solution was neutralized with 1N hydrochloric acid and extracted with chloroform. The extract was dried over anhydrous sodium sulfate. The chloroform was removed under reduced pressure, and the residue was recrystallized from a mixed solvent of ethanol and aqueous ammonia. The resulting crystals were collected by filtration, washed with ethanol, and dried to yield 83 mg of the titled compound as a pale yellow crystal.

1. temperaturewas heated at 100° to 120° C. for 1 hour
2. customdimethyl sulfoxide was removed under reduced pressure
3. additionWater was added to the residue
4. filtrationthe precipitated yellow crystals were collected by filtration
5. stirringThree milliliters of trifluoroacetic acid was stirred under ice-
6. temperaturecooling
7. additionthe above-obtained yellow crystals were slowly added
8. stirringby stirring at room temperature for 30 minutes
9. customThe trifluoroacetic acid was removed under reduced pressure
10. dissolutionthe residue was dissolved in a 1N sodium hydroxide aqueous solution (pH 12)
11. extractionextracted with chloroform
12. dry with materialThe extract was dried over anhydrous sodium sulfate
13. customThe chloroform was removed under reduced pressure
14. customthe residue was recrystallized from a mixed solvent of ethanol and aqueous ammonia
15. filtrationThe resulting crystals were collected by filtration
16. washwashed with ethanol
17. customdried