反应详情

温度

10 °C

To a suspension of sodium hydride (5.42 g, 226 mmol) (prewashed with pentane) in THF (100 ml) cooled at 10° C. was added ethyl acetoacetate (29.4 g, 226 mmol) while keeping the temperature below 15° C. After completion of addition, the mixture was further stirred for 15 minutes and cooled to 5° C. A solution of 1,2,3-trifluoro-4-nitrobenzene (20 g, 113 mmol) in THF (150 ml) was added while keeping the temperature below 5° C. The mixture was then left to warm up to ambient temperature and stirred for 24 hours. The volatiles were removed under vacuum and the residue was partitioned between ethyl acetate and 2N aqueous hydrochloric acid. The organic layer was washed with water, brine, dried (MgSO4) and evaporated. The residue was dissolved in concentrated hydrochloric acid (650 ml) and acetic acid (600 ml) and the mixture was refluxed for 15 hours. After cooling, the volatiles were removed under vacuum and the residue was partitioned between aqueous sodium hydrogen carbonate (5%) and ethyl acetate. The organic layer was washed with sodium hydrogen carbonate, water, brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography eluting with ethylacetate/petroleum ether (75/25) to give 3-acetylmethyl-1,2-difluoro-4-nitrobenzene (17.5 g, 72%).

1. customthe temperature below 15° C
2. additionAfter completion of addition
3. temperaturecooled to 5° C
4. customthe temperature below 5° C
5. waitThe mixture was then left
6. temperatureto warm up to ambient temperature
7. stirringstirred for 24 hours
8. customThe volatiles were removed under vacuum
9. customthe residue was partitioned between ethyl acetate and 2N aqueous hydrochloric acid
10. washThe organic layer was washed with water, brine
11. dry with materialdried (MgSO4)
12. customevaporated
13. dissolutionThe residue was dissolved in concentrated hydrochloric acid (650 ml)
14. temperatureacetic acid (600 ml) and the mixture was refluxed for 15 hours
15. temperatureAfter cooling
16. customthe volatiles were removed under vacuum
17. customthe residue was partitioned between aqueous sodium hydrogen carbonate (5%) and ethyl acetate
18. washThe organic layer was washed with sodium hydrogen carbonate, water, brine
19. dry with materialdried (MgSO4)
20. customevaporated
21. customThe residue was purified by column chromatography
22. washeluting with ethylacetate/petroleum ether (75/25)