反应详情

温度

65 °C

A solution of 2-Aminopyridine (19.02 g, 0.2 mol) in anhydrous DME (70 mL) was added to 1,3-dichloroacetone (25.39 g, 0.2 mol) to form a slurry in a 250-mL 3-necked round bottomed flask outfitted with a reflux condenser and a N2 line. The mixture heated at 65° C. for 18 h, warmed to 80° C. for 3 h and allowed to cool back to room temperature over 2 h. The DME was removed in vacuo and H2O was added to dissolve the resulting solid. Saturated NaHCO3 was added to basify the solution to a pH to 8 and ethyl acetate was used to extract the product (3×300 mL). Both phases were stored in the freezer overnight. The organic phase was dried over Na2SO4, filtered and concentrated to give an orange solid. The aqueous layer was extracted again with ethyl acetate (2×200 mL), then CH2Cl2 (2×200 mL) and these organic layers were dried over Na2SO4, filtered and concentrated to an orange solid. The two solids were combined and dissolved in hot 5-10% MeOH in CH2Cl2, and allowed to cool. The resulting orange crystals were filtered and washed with cold CH2Cl2. A small amount of ether was added to the mother liquor and scratched and put in the freezer. The resulting solid was filtered cold and washed with cold ether. The two batches of solid were combined and dried in the vacuum oven to yield 4.93 g (14%) of the desired product. 1H NMR (CDCl3) d 4.78 (s, 2H) 6.87 (dd, J=6.6 Hz, J=4.3 Hz, 1H) 7.61 (s, 1H) 8.45 (d, J=6.8 Hz 1H) 8.53 (d, J=1.9 Hz, 1H). MS (APCI) calcd for C7H6ClN3: 167.60; found (M+H+) 168.0.

1. customto form a slurry in a 250-mL 3-necked round bottomed flask
2. customoutfitted with a reflux condenser
3. temperaturewarmed to 80° C. for 3 h
4. temperatureto cool back to room temperature over 2 h
5. customThe DME was removed in vacuo and H2O
6. additionwas added
7. dissolutionto dissolve the resulting solid
8. additionSaturated NaHCO3 was added
9. extractionto extract the product (3×300 mL)
10. customwere stored in the freezer overnight
11. dry with materialThe organic phase was dried over Na2SO4
12. filtrationfiltered
13. concentrationconcentrated
14. customto give an orange solid
15. extractionThe aqueous layer was extracted again with ethyl acetate (2×200 mL)
16. dry with materialCH2Cl2 (2×200 mL) and these organic layers were dried over Na2SO4
17. filtrationfiltered
18. concentrationconcentrated to an orange solid
19. dissolutiondissolved in hot 5-10% MeOH in CH2Cl2
20. temperatureto cool
21. filtrationThe resulting orange crystals were filtered
22. washwashed with cold CH2Cl2
23. additionA small amount of ether was added to the mother liquor
24. filtrationThe resulting solid was filtered cold
25. washwashed with cold ether
26. customdried in the vacuum oven