反应详情

温度

90 °C

2-Bromo-3-methyl-4-nitro-phenol, (100 g, 0.43 mol, Intermediate 72) was dissolved in acetone (500 mL), grinded K2CO3, 119 g (0.86 mol) and methyl iodide, 83 g (0.59 mol) were added and the reaction mixture was heated at reflux for one hour. The suspension was filtered and the solvent was removed at reduced pressure to give a brown spontaneously crystallizing oil that was used directly in the next synthetic step. Quantitative yield. The crude methoxy ether, 106 g (0.43 mol) was dissolved in dry DMF (350 mL), dimethylformamid dimethylacetal[DMFDMA], 103 g (0.87 mol) was added and the reaction was heated and stirred at 90° C. for two days. During the next three days were each day a portion of DMFDMA, 20 g (0.17 mol) added while the mixture was continued to be heated. The solvent was removed at reduced pressure and the black/red oily residue was dissolved in HOAc (300 mL). The viscous solution was carefully added to a well stirred suspension of iron powder, 72 g (1.3 mol) in warm HOAc (700 mL) at such rate the exothermic reaction allowed. The thick reaction mixture was heated at reflux for one hour, the solids were filtered of and the solvent was removed at reduced pressure. The black residue was dissolved in warm CHCl3 (700 mL), heptane (600 mL) and 50 g of silica gel was added, the mixture was filtered through a pad of silica, washed with 50/50 CHC13/heptane and the solvent was again removed at reduced pressure. The black residue was chromatographed on a column of silica with petroleum ether/EtOAc 90/10 as eluent to give 14.9 g (15%) of the target compound as a olive green solid. MS (ESI+) for C9H8BrNO m/z 226/228 (M+H)+.

1. additionwere added
2. temperaturethe reaction mixture was heated
3. temperatureat reflux for one hour
4. filtrationThe suspension was filtered
5. customthe solvent was removed at reduced pressure
6. customto give a brown
7. customspontaneously crystallizing oil that
8. dissolutionThe crude methoxy ether, 106 g (0.43 mol) was dissolved in dry DMF (350 mL)
9. additiondimethylformamid dimethylacetal[DMFDMA], 103 g (0.87 mol) was added
10. temperaturethe reaction was heated
11. waitDuring the next three days were each day
12. additiona portion of DMFDMA, 20 g (0.17 mol) added while the mixture
13. temperatureto be heated
14. customThe solvent was removed at reduced pressure
15. dissolutionthe black/red oily residue was dissolved in HOAc (300 mL)
16. additionThe viscous solution was carefully added to a well
17. stirringstirred
18. additionsuspension of iron powder, 72 g (1.3 mol) in warm HOAc (700 mL) at such rate
19. customthe exothermic reaction
20. temperatureThe thick reaction mixture was heated
21. temperatureat reflux for one hour
22. filtrationthe solids were filtered of and the solvent
23. customwas removed at reduced pressure
24. dissolutionThe black residue was dissolved in warm CHCl3 (700 mL)
25. additionheptane (600 mL) and 50 g of silica gel was added
26. filtrationthe mixture was filtered through a pad of silica
27. washwashed with 50/50 CHC13/heptane
28. customthe solvent was again removed at reduced pressure
29. customThe black residue was chromatographed on a column of silica with petroleum ether/EtOAc 90/10 as eluent