反应详情

温度

83 °C

Prepare a solution of 22 g (0.12 mol) of 2,4,6-trichloropyrimidine 1, in 95.2 g (110 mL) of toluene and charge it to the 125 mL addition funnel. Charge a nitrogen-flushed 500 mL round bottom 4-neck flask that equipped with a condenser, heating mantle, thermocouple, 125 mL addition funnel, mechanical stirrer and nitrogen inlet/outlet with 62.7 g (63 mL, 0.72 mol) of morpholine 2, 95.2 g (110 mL) of toluene and 44 g (44 mL) of water. Add the toluene solution of 1 over 10 minutes. Heat the reaction mixture to 83±3° C. Stir at 83±3° C. for 2 h. Check the progress of the reaction. Cool to 30±3° C. Transfer the 2-phase mixture to a 1 L separatory funnel. Separate the phases. Wash the organic phase (top) twice with 200 mL (2×100 mL) of warm (30° C.) water. Separate the phases after each wash. Transfer the organic (top) phase back to the 500 mL reaction flask that equipped with a condenser, heating mantle, thermocouple, 125 mL addition funnel, mechanical stirrer and nitrogen inlet/outlet. Stir and add 50.0 mL of 10.0 N aqueous hydrochloric acid solution. Heat the solution to 53±3° C. and stir for 12-18 h. Check the progress of the reaction. Cool to 22±3° C. Transfer the 2-phase mixture to a 1 L separatory funnel. Separate the phases. Transfer the aqueous (bottom) phase to a 500 mL round bottom 4-neck flask equipped with a cooling bath, thermocouple, addition funnel, pH probe, mechanical stirrer and nitrogen inlet/outlet. Stir and cool to 0±3° C. Add 85.0 g of 25% aqueous sodium hydroxide solution by drops over 30 minutes, maintaining a batch temperature of 10±10° C. throughout the addition. Warm to 20±3° C. and stir for 30 minutes. Isolate the solids by vacuum filtration. Wash the cake with 3×100 mL of water. Dry the solids (55° C., 30 mbar) for 24 hours to afford 30.9 g (91.9% yield) of 3 as a white crystalline solid.

1. additionto the 125 mL addition funnel
2. additionCharge a nitrogen-
3. customflushed 500 mL round bottom 4-neck flask
4. customthat equipped with a condenser
5. temperatureheating mantle
6. customthe progress of the reaction
7. temperatureCool to 30±3° C
8. customSeparate the phases
9. washWash the organic phase (top) twice with 200 mL (2×100 mL)
10. temperatureof warm (30° C.) water
11. customSeparate the phases after each wash
12. customback to the 500 mL reaction flask
13. customthat equipped with a condenser
14. temperatureheating mantle
15. additionthermocouple, 125 mL addition funnel, mechanical stirrer and nitrogen inlet/outlet
16. stirringStir
17. temperatureHeat the solution to 53±3° C.
18. stirringstir for 12-18 h
19. customthe progress of the reaction
20. temperatureCool to 22±3° C
21. customSeparate the phases
22. customTransfer the aqueous (bottom) phase to a 500 mL round bottom 4-neck flask equipped with a cooling bath
23. additionthermocouple, addition funnel
24. stirringStir
25. temperaturecool to 0±3° C
26. additionAdd 85.0 g of 25% aqueous sodium hydroxide solution by drops over 30 minutes
27. temperaturemaintaining a batch temperature of 10±10° C.
28. additionthroughout the addition
29. temperatureWarm to 20±3° C.
30. stirringstir for 30 minutes
31. customIsolate the solids
32. filtrationby vacuum filtration
33. washWash the cake with 3×100 mL of water
34. customDry the solids (55° C., 30 mbar) for 24 hours