反应详情

温度

130 °C

In 150 ml of methanol 8.5 ml (0.15 mol) of 96% sulfuric acid is dissolved under cooling and the solution is then heated under reflux conditions for ½ hour. After cooling to room temperature 20 g (0.0678 mol) of [2-(2-thienyl)ethylamino](2-chlorophenyl)acetamide, falling under general formula (VII) and prepared as described in Example 7, is added to the solution, the mixture is placed into a closed apparatus (autoclave) and stirred in it at 130° C.- on for 5 hours, while the inner pressure elevates to 13 bar. The reaction mixture is then cooled to room temperature (remaining pressure 1-2 bar), the methanol is distilled off in vacuo and to the residue 100 ml of isopropyl acetate and 100 ml of water are added and the pH of the mixture is adjusted to 7.5 by dropwise addition of ˜60 ml of 10% sodium hydroxide solution, under cooling and stirring, while keeping the mixture at room temperature. The phases are separated, the organic phase is stirred with 60 ml of 3% aqueous maleic acid solution at 40-50° C. for 10 minutes, the two phases are then separated. After re-extracting the aqueous maleic acid solution with 30 ml of isopropyl acetate the organic layers are combined, dried over anhydrous sodium sulfate and concentrated to the half of its volume. On addition of 5 ml of conc. hydrochloric acid solution the product precipitates as an oil which crystallizes within a few minutes. It is cooled to 0-(+5)° C. and after 2 hours the crystals are collected by filtration, washed with a small amount of isopropyl acetate and dried. Weight: 19.4 g (82.5%) mp.: 177-178° C. The quality of the product is identical with that of the material obtained in Example 9.

1. temperatureunder cooling
2. temperaturethe solution is then heated under reflux conditions for ½ hour
3. customprepared
4. additionis added to the solution
5. temperatureThe reaction mixture is then cooled to room temperature (remaining pressure 1-2 bar)
6. distillationthe methanol is distilled off in vacuo and to the residue 100 ml of isopropyl acetate and 100 ml of water
7. additionare added
8. additionthe pH of the mixture is adjusted to 7.5 by dropwise addition of ˜60 ml of 10% sodium hydroxide solution
9. temperatureunder cooling
10. stirringstirring
11. customat room temperature
12. customThe phases are separated
13. stirringthe organic phase is stirred with 60 ml of 3% aqueous maleic acid solution at 40-50° C. for 10 minutes
14. customthe two phases are then separated
15. extractionAfter re-extracting the aqueous maleic acid solution with 30 ml of isopropyl acetate the organic layers
16. dry with materialdried over anhydrous sodium sulfate
17. concentrationconcentrated to the half of its volume
18. additionOn addition of 5 ml of conc. hydrochloric acid solution the product
19. customprecipitates as an oil which
20. customcrystallizes within a few minutes
21. temperatureIt is cooled to 0-(+5)° C
22. filtrationand after 2 hours the crystals are collected by filtration
23. washwashed with a small amount of isopropyl acetate
24. customdried