反应详情

2-(6-Methoxy-pyridin-3-yl)-malonic acid diethyl ester (5.6 g, 21.0 mmoL) prepared in Example 3 was dissolved in 2N NaOH/THF:H2O (1:1) (20 mL). The resulting mixture was heated to reflux for 3 hours. The reaction mixture was then adjusted to pH=1 by concentrated HCl and stirred at room temperature for another 1 hour. The solution was then adjusted to pH=13 by 1N NaOH and extracted with ether. The aqueous phase was acidified to pH=5 by 1N HCl and extracted 3× by ethyl acetate. The combined organic phase was then washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give the title compound a white solid (2.45, 70%).

1. temperatureThe resulting mixture was heated
2. temperatureto reflux for 3 hours
3. extractionextracted with ether
4. extractionextracted 3× by ethyl acetate
5. washThe combined organic phase was then washed with brine
6. dry with materialdried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated