Tetrahydrofuran → 2-(4-Bromophenyl)-1,1-bis(3-(trifluoromethoxy)phenyl)ethanamine

Beteiligte Stoffe

Reaktionsschritte

To a solution of 3-(4-bromophenyl)-2,2-bis(3-(trifluoromethoxy)phenyl)propanoic acid (224 mg, 0.41 mmol) in dioxane (5 mL) was added 4 Å molecular sieves (appx 100 mg), triethylamine (0.068 mL, 0.49 mmol) and diphenylphosphoryl azide (0.11 mL, 0.49 mmol) and the reaction mixture was stirred for 45 minutes. 2-(Trimethylsilyl)ethanol (0.176 mL, 1.23 mmol) was added and the reaction mixture was heated at reflux for 1 h. The reaction mixture was allowed to cool to rt and concentrated under reduced pressure. The residue was diluted with Et2O (10 mL) and washed with sat. NH4Cl (5 mL), sat. NaHCO3 (5 mL) and sat. NaCl (5 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was diluted with THF (5 mL) and cooled in an ice-bath, then a 1M solution of tetrabutylammonium fluoride in THF (0.80 mL, 0.80 mmol) was added dropwise. The reaction mixture was allowed to warm to rt and stirred for 3 h. The reaction mixture was diluted with CH2Cl2 (5 mL) and washed with H2O (5 mL) and sat. NaCl (5 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The resulting residue was purified on ISCO silica chromatography with elution at 0 to 50% EtOAc/hexane to give 2-(4-bromophenyl)-1,1-bis(3-(trifluoromethoxy)phenyl)ethanamine (78 mg, 37% yield) as a clear colorless oil. LCMS: RT=1.87 min [M−NH2] 505.0 (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); NMR: 400 MHz 1H (CDCl3) δ ppm 1.68 (bs, 2H), 3.46 (s, 2H), 6.57 (d, J=8.35 Hz, 2H), 7.10 (d, J=8.35 Hz, 2H), 7.18 (s, 2H), 7.21-7.26 (m, 4H), 7.32 (t, J=8.13 Hz, 2H).

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