反应详情

温度

110 °C

A mixture of 2-bromo-4-fluoro-5-methoxybenzoic acid 1 (1.0 kg, 4.02 mol), 4-bromophenol (4.41 mol, 1.05 equiv, 729.5 g) and Cs2CO3 (12.06 mol, 3 equiv. 3.92 kg) in anhydrous DMF (12 L) was degassed with N2 for 30 min. To this mixture was added copper (I) triflate toluene complex (2:1) (0.04 equiv. 83.12 g) and the mixture was further degassed again with N2 for 15 min. The resulting mixture was heated at 110° C. for 4 days. The reaction mixture was cooled to ambient temperature and poured onto 5 L of ice water. The pH was adjusted to 1 with concentrated HCl and the aqueous layer was extracted with EtOAc (3×4 L). The combined extracts were washed with brine (2×2 L). The organic layer was separated, dried over Na2SO4, filtered and concentrated under reduced pressure to provide a thick brown oil. The brown oil was triturated with a 5% IPA/water mixture (5 L) at ambient temp to obtain a brown solid. The solid was filtered, washed with water and hexane and dried overnight under vacuum to afford 2-(4-bromophenoxy)-4-fluoro-5-methoxybenzoic acid (1.3 kg, 95% yield) as a brown solid.

1. customwas degassed with N2 for 30 min
2. additionTo this mixture was added copper (I) triflate toluene complex (2:1) (0.04 equiv. 83.12 g)
3. customthe mixture was further degassed again with N2 for 15 min
4. temperatureThe reaction mixture was cooled to ambient temperature
5. additionpoured onto 5 L of ice water
6. extractionthe aqueous layer was extracted with EtOAc (3×4 L)
7. washThe combined extracts were washed with brine (2×2 L)
8. customThe organic layer was separated
9. dry with materialdried over Na2SO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customto provide a thick brown oil
13. customThe brown oil was triturated with a 5% IPA/water mixture (5 L) at ambient temp
14. customto obtain a brown solid
15. filtrationThe solid was filtered
16. washwashed with water and hexane
17. customdried overnight under vacuum