反应详情

温度

153 °C

N-(2-Fluoro-4-iodo-phenyl)-acetamide (63 g, 226 mmol) was dissolved in HPMA (100 mL). Copper(1) cyanide (20.6 g, 230 mmol) was added and the mixture heated to an external temperature of 153° C. for 5 h. The hot reaction mixture was poured into water (1 L) with stirring. A large amount of solid formed. The solid was filtered and washed with water (200 mL). The solid was extracted by heating in a flask with methylene chloride (500 mL) for 15 min. The solid was filtered off, washed with methylene chloride (3×100 mL). The combined organic extracts were washed with brine (200 mL), dried over anhydrous sodium sulfate, filtered and concentrated to give a brown-orange solid. Ethanol (100 mL) was added and the mixture heated to reflux. The solid did not all dissolve. The cooled mixture was filtered to give a light brown solid. The filtrate was concentrated to ½ volume and cooled overnight to give a further crop of solid. The combined solids were washed with cold ethanol (30 mL) and dried under vacuum to give 30 g (168 mmol). Yield: 75%; mp 173° C.; 1H NMR (400 MHz, DMSO-d6) δ 10.3 (br s, 1H, NH), 8.3 (t, J=8.2 Hz, 1H), 7.9 (d, J=10.7 Hz, 1H), 7.67 (d, J=10.7 Hz, 1H), 2.16 (s, 3H, Me).

1. customA large amount of solid formed
2. filtrationThe solid was filtered
3. washwashed with water (200 mL)
4. extractionThe solid was extracted
5. temperatureby heating in a flask with methylene chloride (500 mL) for 15 min
6. filtrationThe solid was filtered off
7. washwashed with methylene chloride (3×100 mL)
8. washThe combined organic extracts were washed with brine (200 mL)
9. dry with materialdried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customto give a brown-orange solid
13. temperaturethe mixture heated to reflux
14. filtrationThe cooled mixture was filtered
15. customto give a light brown solid
16. concentrationThe filtrate was concentrated
17. temperaturecooled overnight
18. customto give a further crop of solid
19. washThe combined solids were washed with cold ethanol (30 mL)
20. customdried under vacuum
21. customto give 30 g (168 mmol)