Cesium fluoride → methyl 2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)phenyl)acetate

Temperature

60 °C

In a 200 mL flask, 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (3.45 g, 11.2 mmol), and methyl 2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetate (3.71 g, 13.4 mmol) were diluted with dioxane (45 mL) and water (11 mL). This solution was sparged with nitrogen gas for 10 minutes. Then tri-tert-butylphosphonium tetrafluoroborate (0.325 g, 1.12 mmol), diacetoxypalladium (0.126 g, 0.560 mmol) and cesium fluoride (3.40 g, 22.4 mmol) were added as solids. The flask was sealed and evacuated with vacuum and purged with nitrogen gas. The reaction was warmed to an internal temperature of 60° C. and stirred for 18 hours. The reaction was poured into a brine solution and extracted with ethyl acetate (3×50 mL). The combined organics were dried over magnesium sulfate, filtered, and concentrated. The resulting residue was purified by flash chromatography using 0-10% ethyl acetate/hexanes as eluent to afford the title compound as an off white solid (3.45 g, 82%): 1H NMR (400 MHz, DMSO-d6) δ 9.41 (s, 1H), 8.11-8.04 (m, 4H), 7.63 (ddt, J=7.9, 2.1, 1.1 Hz, 2H), 7.48-7.36 (m, 2H), 3.77 (s, 2H), 3.64 (s, 3H); 19F NMR (376 MHz, DMSO-d6) δ −57.02; ESIMS m/z 378 ([M+H]+)

1. customThis solution was sparged with nitrogen gas for 10 minutes
2. customThe flask was sealed
3. customevacuated with vacuum
4. custompurged with nitrogen gas
5. additionThe reaction was poured into a brine solution
6. extractionextracted with ethyl acetate (3×50 mL)
7. dry with materialThe combined organics were dried over magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe resulting residue was purified by flash chromatography

ORD record

ord-9f9a5bc1a35b428d823c686cc2f31974

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09445594B2