Triethylamine → Ethyl 3-(4-(2-(4-fluoro-3-(trifluoromethyl)benzamido)-2,2-bis(3-(trifluoromethoxy)phenyl)ethyl)phenyl)propanoate

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(4-bromophenyl)-1,1-bis(3-(trifluoromethoxy)phenyl)ethanamine (26 mg, 0.050 mmol) in THF (0.5 mL) was added a 0.5 M solution of 3-ethoxy-3-oxopropylzinc bromide in THF (0.18 mL, 0.090 mmol) followed by tetrakis(triphenylphosphine)palladium(0) (3 mg, 5 mol %). The reaction mixture was heated at 130° C. under microwave irradiation for 0.5 h. The reaction mixture was filtered through silica gel and eluted with THF. The solvents were removed under reduced pressure and the residue was dissolved into CH2Cl2 (0.5 mL) then triethylamine (0.020 mL, 0.15 mmol) was added followed by 4-fluoro-3-(trifluoromethyl)benzoylchloride (0.020 mL, 0.13 mmol). The reaction mixture was stirred at rt for 3 h then diluted with Et2O (10 mL) and the organic layer was washed with sat. NH4Cl (2 mL), sat. NaHCO3 (2 mL) and sat. NaCl (2 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by prep TLC plate, eluting with 20% EtOAc/hexane to give ethyl 3-(4-(2-(4-fluoro-3-(trifluoromethyl)benzamido)-2,2-bis(3-(trifluoromethoxy)phenyl)ethyl)phenyl)propanoate (11 mg, 31% yield) as a clear, colorless oil. LCMS: RT=2.26 min [M+H] 731.93 (2 min Phenomenex Luna C18 column, 4.6×30 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm).

Provenance & Evidence