Pyridine → {2-[4-(3-Trifluoromethyl-phenoxy)-phenyl]ethyl}-carbamic acid tert-butyl ester

Participants

Reaction Steps

4 Å molecular sieves were added to a stirred solution of 3-(trifluoromethyl)phenylboronic acid (2.4 g, 12.643 mmol, 2 eq) and [2-(4-Hydroxy-phenyl)-ethyl]-carbamic acid tert-butyl ester (1.5 g, 6.321 mmol, 1 eq) in dry DCM (68.7 ml) at ambient temperature in a dark flask flushed with dry air. The reaction mixture was stirred for 10 min with a drying tube attached. Copper (II) acetate (1.16 g, 6.385 mmol, 1.01 eq), TEA (4.4 ml, 31.609 mmol, 5 eq) and pyridine (2.55 ml, 31.609 mmol, 5 eq) were added and the reaction mixture was stirred at ambient temperature overnight. The reaction mixture was diluted with 50 ml of Et2O, filtered through celite and washed with 0.5 M HCl. Organic layer was dried over anhydrous Na2SO4, filtered and evaporated to give a crude product. Crude product was purified via Biotage SP-1 Snap Si 50 g; 40 mil/min; in the gradient of EtOAc in Cy: 3% for 1.5 CV, 3-25% for 12 CV; 25-40% for 8 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product {2-[4-(3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (710 mg, yield=22.4%, purity=76%). [M+H]+=382.40 1H NMR (300 MHz; CDCl3) δ/ppm 1.43 (s, 9H), 2.77 (t, J=7.0 Hz, 2H), 3.37 (q, J=6.5 Hz, 2H), 4.58 (br. s., 1H), 6.92-6.97 (m, 1H), 7.06-7.22 (m, 5H), 7.28-7.33 (m, 1H), 7.34-7.45 (m, 1H)

Provenance & Evidence