反应详情

温度

100 °C

In 25 ml of N,N-dimethylformamide was dissolved 2.30 g of 2-(p-toluenesulfonyl)-5-bromoisoindoline, and 1.51 g of silver (I) oxide and 0.75 g of tetrakis(triphenylphosphine)palladium (0) were added to the solution, after which the resulting mixture was stirred at 100° C. for five minutes under a nitrogen atmosphere. Subsequently, to this reaction mixture was added 1.54 g of ethyl 1-cyclopropyl-6-fluoro-8-methyl-7-tributylstannyl-1,4-dihydro-4-oxoquinoline-3-carboxylate dissolved in 5 ml of N,N-dimethylformamide, and resulting mixture was stirred at 100° C. for 15 minutes. The reaction mixture was added to a mixed solvent of 50 ml of ethyl acetate and 100 ml of water, and the pH was adjusted to 2 with 2N hydrochloric acid, after which insolubles were removed by filtration. The organic layer formed was separated, washed with a saturated saline solution and then dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure. The residue obtained was purified by a column chromatography (eluent: toluene:ethyl acetate=3:1), and diethyl ether was thereafter added thereto, after which the crystals formed were collected by filtration, to obtain 0.55 g of colorless, crystalline ethyl 1-cyclopropyl-6-fluoro-8-methyl-7-[2-(p-toluenesulfonyl)isoindolin-5-yl]-1,4-dihydro-4-oxoquinoline-3-carboxylate.

1. additionwere added to the solution
2. customresulting mixture
3. stirringwas stirred at 100° C. for 15 minutes
4. customafter which insolubles were removed by filtration
5. customThe organic layer formed
6. customwas separated
7. washwashed with a saturated saline solution
8. dry with materialdried over anhydrous magnesium sulfate
9. customThe solvent was then removed by distillation under reduced pressure
10. customThe residue obtained
11. customwas purified by a column chromatography (eluent: toluene:ethyl acetate=3:1), and diethyl ether
12. additionwas thereafter added
13. customafter which the crystals formed
14. filtrationwere collected by filtration