反应详情

温度

35 °C

To a solution of 1-(2,3-difluorophenyl)-2-(1-(trityloxy)but-3-en-2-yloxy)ethanone (21.1 g, 0.0435 mol, 1.0 equiv.) in MeOH (106 mL) was added NaOAc (5.36 g, 0.0653 mol, 1.50 equiv.) at ambient temperature. After 5 min., NH2OH HCl (3.33 g, 0.048 mol, 1.10 equiv.) was added in portions. The suspension was warmed to 35° C. and stirred for 1 h. The reaction mixture was cooled to 17.8° C. and stirred for 15 mins, then filtered and rinsed with EtOAc (84 mL). The filtrates were concentrated under vacuum (T<30° C.). To the resulting residue was charged 2-methoxy-2-methylpropane (169 mL) and water (21.1 mL). The organics were washed with sat. aq. NaHCO3 (53 mL) and 18% aq. NaCl (21 mL). The organics were concentrated under vacuum to afford the title compound as an oil (21.0 g). 1H NMR (500 MHz, CDCl3) δ ppm 7.42-7.32 (m, 6H), 7.30-7.15 (m, 10H), 7.16-7.06 (m, 1H), 7.03-6.95 (m, 1H), 5.72-5.58 (m, 1H), 5.24-5.13 (m, 2H), 4.80 (d, J=14.6 Hz, 1H), 4.73 (d, J=14.6 Hz, 1H), 4.45 (d, J=12.4 Hz, 0.3H), 4.35 (d, J=12.4 Hz, 0.3H), 3.99-3.91 (m, 0.3H), 3.91-3.83 (m, 1H), 3.20 (dd, J=9.9, 6.8 Hz, 0.3H), 3.09 (dd, J=9.8, 6.6 Hz, 1H), 3.02 (dd, J=9.9, 4.2 Hz, 0.3H), 2.95 (dd, J=9.8, 4.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ ppm 155.40, 150.59 (dd, JCF=248.1, 13.0 Hz), 148.86 (dd, JCF=252.6, 13.5 Hz), 143.96, 135.10, 128.73, 128.69, 127.72, 127.68, 126.92, 126.85, 124.96, 124.56 (d, JCF=10.6 Hz), 124.03-123.86 (m), 118.64 (d, JCF=15.1 Hz), 117.92 (d, JCF=17.2 Hz), 86.66, 86.50, 81.30, 80.32, 69.20, 66.54, 66.48, 62.57.

1. temperatureThe reaction mixture was cooled to 17.8° C.
2. stirringstirred for 15 mins
3. filtrationfiltered
4. washrinsed with EtOAc (84 mL)
5. concentrationThe filtrates were concentrated under vacuum (T<30° C.)
6. additionTo the resulting residue was charged 2-methoxy-2-methylpropane (169 mL) and water (21.1 mL)
7. washThe organics were washed with sat. aq. NaHCO3 (53 mL) and 18% aq. NaCl (21 mL)
8. concentrationThe organics were concentrated under vacuum