反应详情

To a solution of propan-1-ol (2.94 mL, 39.26 mmol) in DMF (15 mL) at 0° C. was added sodium hydride (95% in mineral oil, 0.94 g, 39.26 mmol) in portions and stirred for 1 h at room temperature. This mixture was slowly added to a solution of 2,6-dichloro-nicotinamide (5.0 g, 26.17 mmol) in DMF (25 mL) at 0° C. The reaction mixture was stirred at room temperature overnight. DMF was removed under reduced pressure, and the resulting mixture was diluted with EtOAc (60 mL), washed with water (2×20 mL) and brine (2×10 mL) solution, dried over anhydrous Na2SO4, filtered, and concentrated to give yellow oil. Purification was accomplished by flash chromatography on silica gel using 5-60% EtOAc/hexanes gradient elution to yield the title compound (3.8 g, 68%) as a transparent oil. 1H NMR (400 MHz, CDCl3) δ ppm 8.46 (d, J=8.2 Hz, 1 H), 7.69 (br. s., 1 H), 7.06 (d, J=8.2 Hz, 1 H), 5.86 (br. s., 1H), 4.48 (t, J=6.6 Hz, 2 H), 1.99-1.79 (m, 2 H), 1.07 (t, J=7.4 Hz, 3 H).

1. stirringThe reaction mixture was stirred at room temperature overnight
2. customDMF was removed under reduced pressure
3. additionthe resulting mixture was diluted with EtOAc (60 mL)
4. washwashed with water (2×20 mL) and brine (2×10 mL) solution
5. dry with materialdried over anhydrous Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customto give yellow oil
9. customPurification
10. washwas accomplished by flash chromatography on silica gel using 5-60% EtOAc/hexanes gradient elution