反应详情

温度

130 °C

Mix 6-[3-(4-acetyl-3-hydroxy-2-propyl-phenoxymethyl)-phenoxy]-nicotinonitrile of Preparation 42, (0.33 g, 0.83 mmol), isopropyl alcohol (5 mL), zinc bromide (1.12 g, 4.98 mmol), sodium azide (0.32 g, 4.98 mmol) and water (5 mL) in a pressure flask. Seal the flask and heat to 130° C. in an oil bath for 6 hr. Allow to cool to ambient temperature and pour into 1N hydrochloric acid (50 mL). Filter the white solid and purify by flash chromatography, using 40:1 chloroformchloroform/methanol+1% acetic acid to 20:1 chloroformchloroform/methanol+1% acetic acid as a gradient eluent to give the title compound (0.25 g, 68%): MS (m/z): 444.2 (M−1). 1H NMR (DMSO-d6) 12.86 (s, 1H), 8.80 (s, 1H), 8.46 (d, J=8.2 Hz, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.52 (t, J=8.2 Hz, 1H), 7.37-7.28 (m, 3H), 7.20 (d, J=8.2 Hz, 1H), 6.75 (d, J=8.8 Hz, 1H), 5.32 (s, 2H), 2.63-2.55 (m, 5H), 1.51-1.41 (m, 2H), 0.82 (t, J=7.2 Hz, 3H).

1. additionMix
2. customSeal the flask
3. temperatureto cool to ambient temperature
4. filtrationFilter the white solid
5. custompurify by flash chromatography