反应详情

温度

90 °C

A dry 100 L glass jacketed reactor equipped with an addition funnel, reflux condenser, solids addition system and temperature probe was charged with 2,5-dibromobenzoic acid (2685 g, 9.6 mol) and copper (I) triflate toluene complex (2:1, 50.0 g, 0.2 mol). Toluene (30 L) and EtOAc (20 mL) were then charged, followed by 2-methoxy-4-fluorophenol (1500 g, 10.6 mol). With vigorous stirring cesium carbonate (6258 g, 19.2 mol) was added in portions. The mixture was heated to 90° C. for 4 hours. The mixture was cooled to 35° C. and water (15 L) was added. After 15 minutes of stirring the phases were separated and the aqueous phase was washed with toluene (7.5 L). With stirring, EtOAc (15.0 L) was added to the aqueous phase, followed by 6 M HCl (5.6 L) keeping the internal temperature below 30° C. The layers were separated and the organics were dried over magnesium sulfate. Filtration through a pad of celite and concentration provided a solid that was reslurried in 915 mL of EtAOc and 9.2 L of heptanes. Stirring was continued for 1 hour before the solids were filtered and washed with heptanes. Drying provided 2560 g of 5-bromo-2-(2-fluoro-4-methoxyphenoxy)benzoic acid as a cream colored solid.

1. customequipped with an addition funnel
2. temperaturereflux condenser
3. additionsolids addition system and temperature probe
4. additionwas added in portions
5. temperatureThe mixture was cooled to 35° C.
6. customwere separated
7. washthe aqueous phase was washed with toluene (7.5 L)
8. stirringWith stirring
9. additionEtOAc (15.0 L) was added to the aqueous phase
10. customthe internal temperature below 30° C
11. customThe layers were separated
12. dry with materialthe organics were dried over magnesium sulfate
13. filtrationFiltration
14. concentrationthrough a pad of celite and concentration
15. customprovided a solid
16. stirringStirring
17. waitwas continued for 1 hour before the solids
18. filtrationwere filtered
19. washwashed with heptanes
20. customDrying