反应详情

温度

80 °C

A mixture of malonic acid dimethyl ester, sodium salt (8.067 g, 52.4 mmol), as prepared in the previous step, 2,6-dichloro-nicotinonitrile (4.53 g, 26.2 mmol), as prepared in Example 6b, and dioxane (40 mL) was stirred at 80° C. for 1 h. The resulting easily stirred reddish-brown opaque thin slurry was allowed to cool to rt, 6 M HCl (aq) (80 mL) was added, and the mixture was vigorously stirred at 65-70° C. for 5 h open to air. The resulting clear dark amber solution containing a small amount of dark material was allowed to cool to rt, diluted with water (80 mL), and extracted with DCM (3×100 mL). The organic layers were combined, dried (2×Na2SO4), and concentrated under reduced pressure at 60° C. to provide the crude title compound as a dark brown oil (6.2 g, quantitative yield). A NMR spectrum of the reaction following malonate addition indicated a ˜1:2 mixture of desired/undesired regioisomers.

1. temperatureto cool to rt
2. stirringthe mixture was vigorously stirred at 65-70° C. for 5 h open to air
3. additionThe resulting clear dark amber solution containing a small amount of dark material
4. temperatureto cool to rt
5. extractionextracted with DCM (3×100 mL)
6. dry with materialdried (2×Na2SO4)
7. concentrationconcentrated under reduced pressure at 60° C.