反应详情

温度

45 °C

Preparation 1 (55.6 g, 292.5 mmol) and 1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (67.3 g, 351 mmol) were added to a solution of crude amine 6 (68.0 g, ca. 234 mmol) and N,N-diisopropylethylamine (184 mL, 1053 mmol) in DMF (1050 mL) and the reaction mixture stirred at 45° C. for 18 h. After this time, the reaction mixture was then diluted with water (2500 mL) and ethyl acetate (2500 mL) and stirred vigorously until the phases cleared. The phases were separated and the aqueous layer extracted with ethyl acetate (2×1 L). The combined organics were sequentially washed with 1 N hydrochloric acid (2500 mL), saturated aqueous sodium carbonate (2500 mL), and then brine (2500 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (silica, eluent: ethyl acetate/heptane) to afford carbamate 8 (43.9 g, 49%) as a light yellow solid: 1H NMR (300 MHz, CDCl3) δ10.49 (s, 1H), 8.27-8.13 (m, 2H), 7.31-7.24 (m, 1H), 3.45 (dd, J=16.4, 1.8 Hz, 1H), 3.22 (s, 3H), 2.95 (d, J=16.4 Hz, 1H), 1.80 (s, 3H), 1.57 (s, 9H); ESI MS m/z 381 [M+H]+. Also afforded 7 (23.9 g, 26%) as a light yellow solid: 1H NMR (300 MHz, CDCl3) δ 10.16 (s, 1H), 8.21 (dd, J=9.1, 2.5 Hz, 1H), 8.09 (d, J=2.5 Hz, 1H), 7.08 (d, J=9.1 Hz, 1H), 3.66 (s, 3H), 3.55 (s, 3H), 2.85 (d, J=15.0 Hz, 1H), 2.74 (d, J=15.0 Hz, 1H), 1.82 (s, 3H), 1.54 (s, 9H); ESI MS m/z 393 [M+H]+.

1. stirringstirred vigorously until the phases
2. customThe phases were separated
3. extractionthe aqueous layer extracted with ethyl acetate (2×1 L)
4. washThe combined organics were sequentially washed with 1 N hydrochloric acid (2500 mL), saturated aqueous sodium carbonate (2500 mL)
5. dry with materialbrine (2500 mL), dried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by column chromatography (silica, eluent: ethyl acetate/heptane)