反应详情

A 125 mL pressure flask was charged with 2-fluoro-5-hydroxypyridine (5.0374 g, 45 mmol), 50 mL water, a stirbar, and sodium carbonate (4 ml, 89 mmol). The slurry was stirred and heated using a heat gun until homogenous. The solution was cooled to room temperature, and treated with iodine (2 ml, 45 mmol). The flask was sealed, and the reaction was stirred overnight at room temperature. The slurry was filtered through a 0.22 μm PTFE membrane, and the precipitate was washed with water (3×30 mL). The precipitate was dried at <1 mm Hg and 60° C. for 12 h, and then heated into 20 mL dry DCE. The cloudy solution was filtered hot, and allowed to cool. The filtrate was acidified to pH 3 with 2 M HCl, during which a precipitate had formed. The precipitate was isolated using a 0.22 μm PTFE membrane, washed with water (3×30 mL), and dried under a stream of nitrogen overnight. The solids were washed with hexanes (3×50 mL), DCM (3×50 mL), and then dried under a stream of nitrogen for 1 h to afford 6-fluoro-2-iodopyridin-3-ol (2.88 g, 27% yield). 1H NMR (400 MHz, acetone) δ ppm 6.93 (ddd, J=8.56, 3.57, 0.29 Hz, 1H) 7.38 (ddd, J=8.58, 6.58, 0.39 Hz, 1H) 9.39 (br. s., 1H). 19F NMR (377 MHz, acetone) δ ppm −78.17 (s, 1 F). 13C NMR (101 MHz, acetone) δ ppm 103.81 (d, J=15.17 Hz, 1 C) 110.35 (d, J=39.45 Hz, 1 C) 127.81 (d, J=7.37 Hz, 1 C) 154.14 (d, J=4.33 Hz, 1 C) 156.76 (d, J=234.95 Hz, 1 C). HPLC-MS: 1.39 min (>99%@215 nm; >99% @254 nm; m/z=239.9, calculated for C5H3FINO+H+=239.9).

1. temperatureheated
2. customThe flask was sealed
3. stirringthe reaction was stirred overnight at room temperature
4. filtrationThe slurry was filtered through a 0.22 μm PTFE membrane
5. washthe precipitate was washed with water (3×30 mL)
6. customThe precipitate was dried at <1 mm Hg and 60° C. for 12 h
7. temperatureheated into 20 mL dry DCE
8. filtrationThe cloudy solution was filtered hot
9. temperatureto cool
10. customhad formed
11. customThe precipitate was isolated
12. washwashed with water (3×30 mL)
13. customdried under a stream of nitrogen overnight
14. washThe solids were washed with hexanes (3×50 mL), DCM (3×50 mL)
15. customdried under a stream of nitrogen for 1 h