反应详情

温度

24 °C

To a 2-L, 3-necked, round-bottomed flask equipped with a mechanical stirrer, a thermo couple, and a condenser was added DMF (194 mL), ethyl 6-chloronicotinate (100.00 g, 0.522 mol), and 4-fluorophenol (65.09 g, 0.575 mol). A brown solution formed after stirring for 5-10 min. To the solution was then added Cs2CO3 (189.19 g, 0.575 mol) in one portion. The reaction temperature increased from 20° C. to 30° C. over 10 min without external heating and then started cooling down. The resulting suspension was stirred at rt for 2-3 h and the internal reaction temperature cooled back to 23-25° C. The reaction mixture was then heated to 60° C. and stirred for 18-20 h. HPLC analysis indicated that the reaction was complete. The heating mantle was removed and the reaction mixture was allowed to cool to 25-30° C. To the mixture was added deionized water (145.5 mL) in a steady stream over 5 min and a slight exotherm was observed. The resulting suspension was stirred at rt for 15-20 min. Two additional portions of deionized water (145.5 mL each) were added and the suspension was stirred at rt for 15-30 min. The pH of the suspension was around 9-10. The solid product was collected by vacuum filtration, rinsed thoroughly with deionized water in portions. The filter cake as dried in a filter funnel by pulling through air for 24 h. The product was isolated as a white solid (133.6 g). mp: 68.0° C. (by DSC). 1H NMR (CDCl3): δ 8.81 (d, J=2.6 Hz, 1H), 8.22 (dd, J=8.5, 2.6 Hz, 1H), 7.12 (br s, 2H), 7.10 (d, J=1.0 Hz, 2H), 6.94 (d, J=8.5 Hz, 1H), 4.38 (q, J=7.1 Hz, 2H), 4.38 (t, J=7.1 Hz, 3H). MS (ESI): M+H+=262.1.

1. customA brown solution formed
2. temperatureThe reaction temperature increased from 20° C. to 30° C. over 10 min
3. temperaturewithout external heating
4. temperaturestarted cooling down
5. stirringThe resulting suspension was stirred at rt for 2-3 h
6. temperatureThe reaction mixture was then heated to 60° C.
7. stirringstirred for 18-20 h
8. customThe heating mantle was removed
9. temperatureto cool to 25-30° C
10. additionTo the mixture was added deionized water (145.5 mL) in a steady stream over 5 min
11. stirringThe resulting suspension was stirred at rt for 15-20 min
12. additionTwo additional portions of deionized water (145.5 mL each) were added
13. stirringthe suspension was stirred at rt for 15-30 min
14. filtrationThe solid product was collected by vacuum filtration
15. washrinsed thoroughly with deionized water in portions
16. customThe filter cake as dried in a filter funnel
17. waitby pulling through air for 24 h