反应详情

Malonic acid monoethyl ester (26 g, 199 mmol) was dissolved in tetrahydrofuran (500 ml) and cooled to -70°. After the addition of n-butyllithium (112.5 ml of a 1.6M solution in hexanes, 180 mmol), the reaction mixture was allowed to warm to -10°, and additional n-butyllithium was added (112.5 ml, as above). The resulting milky-white mixture was cooled to -70°, and treated with 2-chloro-4,5-difluorobenzoyl chloride (19 g, 90 mmol) in tetrahydrofuran (200 ml). After warming to room temperature, the reaction mixture was allowed to stir for an additional 2 hours, then poured into 2N hydrochloric acid (750 ml). The aqueous mixture was extracted with ethyl ether, and the combined organic layers were dried and concentrated to provide the title product as a light amber oil (20.6 g, 78.6 mmol, 87% yield), which was used without further purification.

1. temperaturecooled to -70°
2. temperatureto warm to -10°
3. temperatureThe resulting milky-white mixture was cooled to -70°
4. extractionThe aqueous mixture was extracted with ethyl ether
5. customthe combined organic layers were dried
6. concentrationconcentrated