Diethyl Ether → (4-Fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-bromo-3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)benzene (15 g, 51.7 mmol) in Et2O (100 mL) was added n-BuLi (20.7 mL, 2.5 M, 51.7 mmol) at −75° C. The reaction mixture was allowed to warm up to −60° C., followed by the addition of 4-fluoro-3-methoxy-benzonitrile (7.5 g, 46.6 mmol) in a mixture of THF and Et2O (6 mL/6 mL). The reaction was quenched immediately by addition of H2O. The aqueous portion was extracted with Et2O. The separated organic portion was washed by 1N HCl, concentrated under reduced pressure and purified by ISCO chromatography using hexanes/EtOAc (0-10%) to afford (4-fluoro-3-methoxyphenyl)(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)methanone as white powder (13 g, 71%). LCMS: RT=4.101 min, [M+H] 345.1 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 4 minutes containing 0.1% TFA; 4 mL/min, monitoring at 220 nm)

Provenance & Evidence