Sodium hydride → Methyl 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoate

Participants

Reaction Conditions

Reaction Steps

To a suspension of NaH (60% in oil, 66 mg, 1.65 mmol) in DMF (3 mL) at 0° C. was added a solution of methyl 2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)acetate (600 mg, 1.34 mmol) in one portion. The reaction mixture was stirred at 0° C. for 10 min followed by addition of a solution of 4-bromobenzylbromide (343 mg, 1.37 mmol) in DMF (2 mL). The reaction was stirred at 0° C. for 5 min and quenched by the addition of saturated NH4Cl. The mixture was extracted with EtOAc (2×30 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated to give methyl 3-(4-bromophenyl)-2-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)propanoate as a colorless oil (865 mg, 100% yield). LCMS: RT=2.26 min, no ionization (Phenomenex Luna C18 4.6×30 mm column, eluting with 10-90% MeOH/H2O containing 0.1% TFA, 2 min gradient, flow rate 5 mL/min, wavelength 220 nm); HPLC: RT=4.48 min (Phenomenex Luna C18 4.6×50 mm column, eluting with 10-90% MeOH/H2O containing 0.2% PPA, flow rate 4 mL/min, wavelength 220 nm); 1H NMR (400 MHz, CDCl3) δ ppm 7.29-7.33 (1H, m), 7.21-7.27 (4H, m), 7.11 (1H, t, J=9.23 Hz), 6.94 (1H, d, J=8.79 Hz), 6.82 (1H, d, J=9.67 Hz), 6.80 (1H, s), 6.52 (2H, d, J=8.35 Hz), 5.87 (1H, t, J=53.2 Hz), 3.75 (3H, s), 3.56-3.66 (2H, m).

Provenance & Evidence