反应详情

温度

25 °C

To tert-butyl 2-(2-fluoro-3-hydroxy-6-nitrophenyl)-3-oxobutanoate in dichloromethane from above was added further dichloromethane (123 l) followed by trifluoroacetic acid (158 kg) whilst maintaining the temperature at 25° C. The reaction was stirred for 20 hours. The mixture was distilled, removing 283 kg of distillate. Toluene (176 l) was added and the mixture distilled, removing 208 kg of distillate. Further toluene (176 l) was added and the mixture distilled, removing 133 kg of distillate. To the residue was added 7.4% w/w aqueous sodium hydroxide (˜705 kg) until the mixture was pH 10.5. The aqueous layer was separated and washed with toluene (250 l). The aqueous layer was diluted with water (250 l), heated to 40° C. and acetic acid (191.4 kg) added, reducing the pH from 10.1 to 3.8. The pH was then adjusted to 1 with 20% w/w sulphuric acid (˜315 kg). The mixture was cooled to 0° C. and seeded with 1-(2-fluoro-3-hydroxy-6-nitrophenyl)-propan-2-one. Further water (600 kg) was added and the solid isolated by filtration. The filter cake was washed with water (300 l). The product was dried under vacuum (50 mbar) at 40° C. Yield: 56.0 kg, 74% based on 1,2,3-trifluoro-4-nitrobenzene.

1. distillationThe mixture was distilled
2. customremoving 283 kg of distillate
3. additionToluene (176 l) was added
4. distillationthe mixture distilled
5. customremoving 208 kg of distillate
6. additionFurther toluene (176 l) was added
7. distillationthe mixture distilled
8. customremoving 133 kg of distillate
9. additionTo the residue was added 7.4% w/w aqueous sodium hydroxide (˜705 kg) until the mixture
10. customThe aqueous layer was separated
11. washwashed with toluene (250 l)
12. additionThe aqueous layer was diluted with water (250 l)
13. temperatureheated to 40° C.
14. additionacetic acid (191.4 kg) added
15. temperatureThe mixture was cooled to 0° C.
16. additionFurther water (600 kg) was added
17. customthe solid isolated by filtration
18. washThe filter cake was washed with water (300 l)
19. customThe product was dried under vacuum (50 mbar) at 40° C