反应详情

温度

0 °C

Sodium hydride (0.073 g, 3.0 mmol) was stirred in 4 mL anhydrous DMF under Ar. The solution was cooled to 0° C. and 3-iodo-5-hydroxypyridine (0.305 g, 1.38 mmol) was added gradually. After bubbling had subsided N-chloropropylpiperidine hydrochloride (0.330 g, 1.67 mmol) was added slowly. The reaction was then allowed to warm to ambient temperature. After 40 h the reaction was diluted with water and extracted 3× with EtOAc. The combined organic phases were washed was washed with saturated NaCl (aq), dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography (2×16 cm silica, 9:1 CH2Cl2/MeOH) afforded 192 mg 5-iodo-1-(3-piperidin-1-yl-propyl)-1H-pyridin-2-one (18) (40% yield). 1H NMR (CDCl3) δ7.72 (d, J=2.6 Hz, 1H), 7.40 (dd, J=2.6, 9.5 Hz, 1H), 6.37 (d, J=9.5 Hz, 1H), 3.96 (t, J=6.6 Hz, 2H), 2.35 (bs, 4H), 2.26 (t, J=6.6 Hz, 2H), 1.92 (t, 6.6 Hz, 2H), 1.60 (m, 4H), 1.46 (m, 2H).

1. customAfter bubbling
2. additionwas added slowly
3. temperatureto warm to ambient temperature
4. extractionextracted 3× with EtOAc
5. washThe combined organic phases were washed
6. washwas washed with saturated NaCl (aq)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. concentrationconcentrated
10. customPurification by flash column chromatography (2×16 cm silica, 9:1 CH2Cl2/MeOH)