反应详情

A three-neck RBF equipped with a reflux condenser and overhead stirrer was charged with 2-fluoro-4-methoxyphenol (14.24 g, 100 mmol), 2,5-dibromobenzoic acid (25.5 g, 91 mmol), EtOAc (0.446 mL, 4.55 mmol), copper (I) triflate toluene complex (2:1) (0.484 g, 2.27 mmol) and toluene (300 mL). Cesium carbonate (59.4 g, 182 mmol) was carefully added portion-wise. The mixture was stirred for 10 minutes at RT then heated at 95° C. for 3 hours. The toluene was cooled to RT then extracted twice with 300 ml of water. The combined water extracts were acidified with 6 N HCl at which time a precipitate formed. The mixture was extracted with EtOAc (3×500 mL) and the combined organic fractions were dried over sodium sulfate and concentrated in vacuo. The resulting solid was triturated with minimal 1:1 Hexanes:EtOAc and filtered. The collected solid was dried in vacuo to afford 5-bromo-2-(2-fluoro-4-methoxyphenoxy)benzoic acid as a grey solid. The mother liquors were set aside for later recrystallizatio. MS m/z=341.0 [M+H].

1. customA three-neck RBF equipped with a reflux condenser and overhead stirrer
2. temperaturethen heated at 95° C. for 3 hours
3. extractionthen extracted twice with 300 ml of water
4. customformed
5. extractionThe mixture was extracted with EtOAc (3×500 mL)
6. dry with materialthe combined organic fractions were dried over sodium sulfate
7. concentrationconcentrated in vacuo
8. customThe resulting solid was triturated with minimal 1:1 Hexanes
9. filtrationEtOAc and filtered
10. customThe collected solid was dried in vacuo