反应详情

温度

100 °C

To a solution of cis 4-(4-bromo-2-fluorobenzyl)-2,6-dimethylmorpholine (0.76 g, 2.5 mmol) in 1,4-dioxane (7.5 mL) under nitrogen was added ethyl urethane (1.2 mL, 10.0 mmol) followed by portionwise addition of sodium hydride (60% dispersion in mineral oil, 0.40 g, 10.0 mmol). The reaction mixture was heated at 100° C. for 24 h then partitioned between DCM and water and the phases were separated. The aqueous phase was further extracted with DCM and the combined organic layers were dried over sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography (silica, 80 g column, ISCO, 0-100% ethyl acetate in pentane) to afford the title compound (0.114 g, 14%). 1H NMR (CD3OD and CDCl3, 300 MHz): 7.22 (d, J=8.0 Hz, 1H), 7.05 (dd, J=8.1, 1.9 Hz, 1H), 6.97 (d, J=1.9 Hz, 1H), 4.01 (q, J=7.0 Hz, 2H), 3.75-3.62 (m, 2H), 3.47 (s, 2H), 2.75-2.66 (m, 2H), 1.86-1.76 (m, 2H), 1.41 (t, J=7.0 Hz, 3H), 1.14 (d, J=6.3 Hz, 6H). LCMS (Method G): RT=3.24 min, M+H÷=328.

1. customthen partitioned between DCM and water
2. customthe phases were separated
3. extractionThe aqueous phase was further extracted with DCM
4. dry with materialthe combined organic layers were dried over sodium sulfate
5. filtrationfiltered
6. customevaporated
7. customThe residue was purified by flash chromatography (silica, 80 g column, ISCO, 0-100% ethyl acetate in pentane)