反应详情

温度

100 °C

To 16.4 g (53.8 mmol) of ethyl 2,4,5-trifluoro-3-methyl-6-nitrobenzoylacetate were added 17.9 ml (107.6 mmol) of ethyl orthoformate and 29 ml of acetic anhydride, followed by 2 hours of stirring at 100° C. The solvent was evaporated, and the resulting residue was dissolved in 200 ml of toluene and mixed with 16 g (64.7 mmol) of p-toluenesulfonic acid salt of (1R,2S)-2-fluorocyclopropylamine. With cooling in an ice bath, thereto was added dropwise 10.87 ml (78 mmol) of triethylamine dissolved in 30 ml of toluene. After completion of the dropwise addition, this was stirred for 2 hours at the same temperature. The reaction solution was mixed with 200 ml of ethyl acetate and washed with water (500 ml×1) and saturated brine (500 ml×2) in that order. The organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated. The resulting residue was dissolved in 150 ml of 1,4-dioxane. Thereto was subsequently added 3.23 g (80.7 mmol) of sodium hydride in small portions under ice cooling. After 1 hour of stirring at room temperature, the reaction solution was poured into 0.5N hydrochloric acid which was cooled in an ice bath. The thus formed crystals were collected by filtration, washed with water (100 ml×3) and then recrystallized from chloroform-ethanol to yield 13.9 g (70%) of the title compound.

1. customThe solvent was evaporated
2. dissolutionthe resulting residue was dissolved in 200 ml of toluene
3. temperatureWith cooling in an ice bath
4. additionAfter completion of the dropwise addition
5. stirringthis was stirred for 2 hours at the same temperature
6. washwashed with water (500 ml×1) and saturated brine (500 ml×2) in that order
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. customthe solvent was evaporated
9. dissolutionThe resulting residue was dissolved in 150 ml of 1,4-dioxane
10. stirringAfter 1 hour of stirring at room temperature
11. temperaturewas cooled in an ice bath
12. filtrationThe thus formed crystals were collected by filtration
13. washwashed with water (100 ml×3)
14. customrecrystallized from chloroform-ethanol