Tetrahydrofuran → 3-Chloro-5-[(2,6-difluoro-3-methylphenyl)oxy]benzonitrile

Participants

Reaction Conditions

Reaction Steps

A 1M solution KOtBu in THF (4.41 mL, 4.41 mmol) was added to a solution of 2,6-difluoro-3-methylphenol (3 g, 20.82 mmol) in DMSO (10 mL) at 0° C. under an atmosphere of nitrogen. After 10 min, 3-chloro-5-fluorobenzonitrile (3.24 g, 20.82 mmol) and 18-CROWN-6 (0.550 g, 2.082 mmol) were added and the solution was heated to 135° C. After 6 h, the brown solution was cooled to RT and water (100 mL) and ethyl acetate (150 mL) were added. The organic layer was separated, washed with water (2×150 mL), brine (150 mL), dried over MgSO4, filtered and concentrated. The residue was purfied on silica gel (hexanes/ethyl acetate) to give the title compound (4.05 g, 70%) as a white solid (N4011-11-100). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.36 (t, 1H), 7.20 (t, 1H), 7.05-7.14 (m, 2H), 6.93-7.00 (m, 1H), 2.31 (s, 3H).

Provenance & Evidence