Reaktion #325970

Reaktionsgleichung

triethylamine

2-(4-bromophenyl)-1,1-bis(3-(trifluoromethoxy)phenyl)ethanamine

3-ethoxy-3-oxopropylzinc bromide

4-fluoro-3-(trifluoromethyl)benzoylchloride

→

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

Ausbeute 31.0%

Lösungsmittel

Et2O

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe reaction mixture was filtered through silica gel
2. 2
   Wascheneluted with THF
3. 3
   SonstigeThe solvents were removed under reduced pressure
4. 4
   workup.DISSOLUTIONthe residue was dissolved into CH2Cl2 (0.5 mL)
5. 5
   Waschenthe organic layer was washed with sat. NH4Cl (2 mL), sat. NaHCO3 (2 mL) and sat. NaCl (2 mL)
6. 6
   TrocknenThe organic layer was dried over Na2SO4
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated under reduced pressure
9. 9
   SonstigeThe residue was purified by prep TLC plate
10. 10
    Wascheneluting with 20% EtOAc/hexane

Vorschrift

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).

Quelle