反应详情

To a stirred solution of 2-(3,5-difluoro-pyridin-2-yl)-malonic acid diethyl ester (1 g, 3.56 mmol) (Preparation 264) in THF (15 mL) was added a solution of lithium hydroxide monohydrate (462 mg, 10.4 mmol) in water (4 mL) dropwise at 0° C. and the mixture heated to reflux for 2 hours. The reaction mixture was cooled to room temperature, acidified (pH ˜3) with 2N hydrochloric acid and extracted with 20% isopropanol-dichloromethane (5×20 mL). The combined organic layers were dried (Na2SO4) and evaporated in vacuo. The crude material was purified by column chromatography on silica gel (gradient of DCM: MeOH 100:0 to 95:5) to afford the title compound as a solid in 53% yield, 336 mg.

1. temperaturethe mixture heated
2. temperatureto reflux for 2 hours
3. extractionextracted with 20% isopropanol-dichloromethane (5×20 mL)
4. dry with materialThe combined organic layers were dried (Na2SO4)
5. customevaporated in vacuo
6. customThe crude material was purified by column chromatography on silica gel (gradient of DCM: MeOH 100:0 to 95:5)