Cesium carbonate → HCID 57582351, compound

Temperature

80 °C

To a solution of 2-bromo-4-fluorophenol (50.0 g, 261 mmol) in 300 ml of DMF was added Cs2CO3 (213 g, 654 mmol) and heated the reaction mixture for 3 h at 80° C., after that tetrahydrofuran-3-yl methanesulfonate (Int-68) (43.5 g, 261 mmol) was added at room temperature, stirred the reaction mixture for 16 h at 80° C. filtered the base, filtrate was dissolved with EtOAc (1.2 L), washed with water and 1N NaOH solution (800 ml), water and brine solution, dried over sodium sulfate and concentrated to dryness to afford crude compound. This was purified over 60-120 mesh silica using 10-12% ethyl acetate and hexane as an eluent to get the pure product (50 g, yield 73%). 1H NMR (300 MHz, CDCl3) δ 7.32-7.26 (m, 1H), 7.00-6.93 (m, 1H), 6.82-6.77 (m, 1H), 4.91-4.87 (m, 1H), 4.07-3.96 (m, 3H), 3.94-3.89 (m, 1H), 2.20-2.13 (m, 2H).

1. filtrationfiltered the base, filtrate
2. dissolutionwas dissolved with EtOAc (1.2 L)
3. washwashed with water and 1N NaOH solution (800 ml), water and brine solution
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated to dryness
6. customto afford crude compound
7. customThis was purified over 60-120 mesh silica using 10-12% ethyl acetate and hexane as an eluent

ORD record

ord-63274627d56940099a155ddfd9bf8dc2

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394305B2