反应详情

N-(4-Fluorophenyl)-N′-(2-fluoro-4-hydroxyphenyl)cyclopropane-1,1-dicarboxamide (665 mg) was dissolved in N-methylpyrrolidone (10 ml) under a nitrogen atmosphere, and potassium tert-butoxide (247 mg) was added at room temperature, followed by stirring for 1.5 hr. After 4-chloropicolylamide (313 mg) was added, the reaction mixture was stirred under a nitrogen atmosphere at 110° C. overnight, then at 120° C. for 8 hr. The reaction mixture was allowed to cool down to room temperature. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (twice) and brine, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; heptane:ethyl acetate=1:2, 1:3, then 1:4). Fractions containing the target compound were concentrated under reduced pressure. After ethyl acetate (3 ml)-heptane (6 ml) was added, crystals were allowed to precipitate under sonication. The solvent was removed and the crystals were dried under reduced pressure to provide the titled compound as pale brown crystals (261 mg, 29%).

1. stirringthe reaction mixture was stirred under a nitrogen atmosphere at 110° C. overnight
2. waitat 120° C. for 8 hr
3. customThe reaction mixture was partitioned between ethyl acetate and water
4. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (twice) and brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationThe solvent was concentrated under reduced pressure
7. customthe residue was purified by silica gel column chromatography (eluent
8. additionFractions containing the target compound
9. concentrationwere concentrated under reduced pressure
10. additionAfter ethyl acetate (3 ml)-heptane (6 ml) was added
11. customto precipitate under sonication
12. customThe solvent was removed
13. customthe crystals were dried under reduced pressure