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 sping and the aqueous phase was washed with toluene (7.5 L). With stirring, EtOAc (15.0 L) was added to the rich aqueous phase, followed by 6 M HCl (5.6 L) keeping the internal temperature below 30° C. The layers were separated and the organic layers were dried over magnesium sulfate, filtered through a pad of celite and concentration to provide a solid that was re-slurried in 915 mL of EtOAc and 9.2 L of heptanes. Stirring was continued for 1 hour before the solids were filtered and washed with heptanes. The resulting solids were dired to provide 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. washthe aqueous phase was washed with toluene (7.5 L)
7. stirringWith stirring
8. additionEtOAc (15.0 L) was added to the rich aqueous phase
9. customthe internal temperature below 30° C
10. customThe layers were separated
11. dry with materialthe organic layers were dried over magnesium sulfate
12. filtrationfiltered through a pad of celite and concentration
13. customto provide a solid
14. stirringStirring
15. waitwas continued for 1 hour before the solids
16. filtrationwere filtered
17. washwashed with heptanes