反应详情

温度

70 °C

11.25 g (263 mmol; 1.05 eq) of cyanamide was placed is isopropanol (800 ml per tool of ethyl trifluoroacetoacetate; EtTFAA) at 50° C. and HCl gas (18.3 g; 500 mmol; 2.0 eq) was passed through the mixture for one hour. When the introduction of HCl had ended, the mixture was stirred for 2 hours at 70° C. It was then allowed to cool to room temperature and 3/4 of the solvent was evaporated off on a rotary evaporator. 80 ml of water (320 ml per mol of ethyl trifluoroacetoacetate) was added at room temperature to the O-isopropylisourea hydrochloride formed. Aqueous NaOH solution (78.87 g; 1.09 eq; 14 percent according to titration) was then added over 5 minutes at room temperature until the pH had shifted from 0.5 to 11.5, and stirring was continued for 15 minutes. The temperature was kept at ≤30° C. during the addition of the NaOH. Ethyl trifluoroacetoacetate (46.5 g; 500 mmol; 1.0 eq) was then added dropwise to this solution at room temperature. The temperature rose to 30° C. during this process and two phases formed. This mixture was refluxed for 2 hours. The organic solvents were then distilled off until the top temperature reached ca. 96° C. Stirring was continued for 2 hours at 85° to 90° C. The light yellow emulsion was allowed to cool to room temperature, the pH of 7.3 was adjusted to 5.0 with a small amount of 2 N aqueous HCl solution and the granular solid was filtered off after 20 minutes at room temperature. The moist solid obtained after filtration was taken up again with distilled water (~1 g moist product/ml water) and refluxed for 1 hour. After cooling to room temperature, filtration and drying, a light yellowish solid of relatively high content was obtained: the total yield was 67.8 percent (content: 98.0 percent according to HPLC). The solid was washed with a small amount of cold water and then dried overnight in a vacuum drying cabinet at 40° C. 41.3 g of a yellowish solid was obtained as the product, corresponding to a yield of 69.8 percent (content: 94.5 percent according to HPLC).

1. customat 50° C.
2. temperatureto cool to room temperature
3. custom3/4 of the solvent was evaporated off on a rotary evaporator
4. addition80 ml of water (320 ml per mol of ethyl trifluoroacetoacetate) was added at room temperature to the O-isopropylisourea hydrochloride
5. customformed
6. stirringstirring
7. waitwas continued for 15 minutes
8. customrose to 30° C. during this process and two phases
9. customformed
10. temperatureThis mixture was refluxed for 2 hours
11. distillationThe organic solvents were then distilled off until the top temperature
12. customreached ca. 96° C
13. stirringStirring
14. waitwas continued for 2 hours at 85° to 90° C
15. temperatureto cool to room temperature
16. filtrationthe granular solid was filtered off after 20 minutes at room temperature
17. customThe moist solid obtained
18. filtrationafter filtration
19. temperaturerefluxed for 1 hour
20. temperatureAfter cooling to room temperature
21. filtrationfiltration
22. customdrying
23. customa light yellowish solid of relatively high content was obtained
24. washThe solid was washed with a small amount of cold water
25. customdried overnight in a vacuum
26. customdrying cabinet at 40° C