反应详情

Solid potassium tert-butoxide (823 mg) was added to tetrahydrofuran (40 ml) solution of ethyl 6,7,8-trifluoro-1-methylamino-1,4-dihydro-4-oxoquinoline-3-carboxylate (2.0 g) and tert-butyl 2-tert-butoxycarbonylacrylate (1.67 g), with stirring and suspending under ice-cooling, and the suspension was stirred for 0.5 hour with ice-cooling and then 1.5 hours at room temperature. The reaction solution was poured into a mixed liquid of ethyl acetate ice-water (150 ml/150 ml) and was adjusted to have pH of 3.0 with 1N hydrochloric acid. The organic layer was separated out, washed with water and saline solution, and dried over magnesium sulfate. This was concentrated under reduced pressure to obtain an amorphous product. The amorphous product was subjected to column chromatography with silica gel and eluted with a mixed solvent of methylene chloride ethyl acetate (20/1 to 10/1). The fractions containing the object product were collected, and the solvent was removed by distillation under reduced pressure. The residue was tritulated with n-hexane, and the precipitates were filtered out to obtain ethyl 6,7,8-trifluoro-1 -[N-methyl-N-{2,2-bis(tert-butoxycarbonyl)ethyl}amino]-1,4 -dihydro-4-oxoquinoline-3-carboxylate (1.35 g) as an almost white powder.

1. temperaturecooling
2. stirringthe suspension was stirred for 0.5 hour with ice-
3. temperaturecooling
4. custom1.5 hours
5. customat room temperature
6. customThe organic layer was separated out
7. washwashed with water and saline solution
8. dry with materialdried over magnesium sulfate
9. concentrationThis was concentrated under reduced pressure
10. customto obtain an amorphous product
11. washeluted with a mixed solvent of methylene chloride ethyl acetate (20/1 to 10/1)
12. additionThe fractions containing the object product
13. customwere collected
14. customthe solvent was removed by distillation under reduced pressure
15. filtrationthe precipitates were filtered out