反应详情

Entire reaction was performed under dry air using syringe septa technique. 4 Å molecular sievies were added to a stirred solution of 4-chloro-3-(trifluoromethyl)phenylboronic acid (5.00 g, 0.022 mmol) and [2-(4-hydroxy-phenyl)-ethyl]-carbamic acid tert butyl ester (2.64 g, 0.051 mol, 2 eq) in dry DCM (120 ml) at ambient temperature in a flame dried flask flushed with dry air. The reaction was stirred for 15 min. After that, copper (II) acetate (5.33 g, 0.010 mol, 1.3 eq), triethylamine (7.34 ml, 0.052 mol, 5 eq) and pyridine (4.25 ml, 0.052 mol, 5 eq) were added in succession and the reaction was stirred for 50 hours. The reaction mixture was sequential washed with 0.5 M HCl (4×250 ml), water (3×150 ml) and brine (1×150 ml). Organic layers were combined, dried over Na2SO4/MgSO4, filtered and evaporated. Crude product was purified on Biotage SP1 Snap Si 100; 40 ml/min in the gradient of EtOAc in Cyclohexan: 0-30% in 25 CV. The appropriate fractions were combined and evaporated in vacuo to give the required product {2-[4-(4-chloro-3-trifluoromethyl-phenoxy)-phenyl]-ethyl}-carbamic acid tert-butyl ester (2.21 g, yield=24%, purity=82%). [M+H]+=416.84 [M+H-56]+=360.27 1H NMR (300 MHz; CDCl3) δ/ppm 1.50 (s, 9H), 2.85 (t, J=6.97 Hz, 2H), 3.38-3.48 (m, 2H), 4.63 (br. S., 1H), 7.01 (d, J=8.57 Hz, 2H), 7.11 (dd, J=8.77, J=2.79 Hz, 1H), 7.25 (d, J=8.57 Hz, 2H), 7.36 (d, J=2.79 Hz, 1H), 7.47 (d, J=8.77 Hz, 1H)

1. customEntire reaction
2. customunder dry air
3. customdried flask
4. customflushed
5. customwith dry air
6. stirringthe reaction was stirred for 50 hours
7. washThe reaction mixture was sequential washed with 0.5 M HCl (4×250 ml), water (3×150 ml) and brine (1×150 ml)
8. dry with materialdried over Na2SO4/MgSO4
9. filtrationfiltered
10. customevaporated
11. customCrude product was purified on Biotage SP1 Snap Si 100
12. customevaporated in vacuo