反应详情

温度

140 °C

A dry mixture of powdered 3-cyano-6-hydroxy-pyridin-2-ol anion, sodium salt (102.34 g, 0.648 mol), as prepared in the previous step, and triethylamine hydrochloride (89.20 g, 0.648 mol) was swirled until the two components appeared completely mixed. This dry mixture was then cooled on an ice bath while POCl3 (150 mL, 1.62 mol) was slowly poured in under air with intermittent swirling. Triethylamine (90.3 mL, 0.648 mol) was then added rapidly in 2 mL portions with frequent manual swirling while cooling on an ice bath. The flask containing the resulting warm dark semi-solid was then fitted with a reflux condenser and CaSO4 drying tube and stirred under air at 140° C. for 20 h. The easily stirred dark brown thick “solution” was then allowed to cool to rt, chilled on an ice bath, diluted with ether (800 mL), and washed with ice (800 mL). The very dark organic layer was washed with ice water (1×1 L), and the aqueous layers were combined and extracted with ether (3×1 L). The combined ether extracts were concentrated under reduced pressure to give a wet orange-brown solid. This was dissolved in DCM (1 L), dried (2×Na2SO4), and concentrated under reduced pressure at 60° C. to afford the title compound as a brown solid (80.7 g, 466 mmol).

1. additionappeared completely mixed
2. additionwas slowly poured in under air with intermittent swirling
3. temperaturewhile cooling on an ice bath
4. additionThe flask containing the resulting
5. temperaturewarm dark semi-solid
6. customwas then fitted with a reflux condenser and CaSO4 drying tube
7. temperatureto cool to rt
8. temperaturechilled on an ice bath
9. washwashed with ice (800 mL)
10. washThe very dark organic layer was washed with ice water (1×1 L)
11. extractionextracted with ether (3×1 L)
12. concentrationThe combined ether extracts were concentrated under reduced pressure
13. customto give a wet orange-brown solid
14. dry with materialdried (2×Na2SO4)
15. concentrationconcentrated under reduced pressure at 60° C.