反应详情

To a solution (1.25 M) of diethyl acetamidomalonate (5.14 g, 23.66 mmol) in N-methyl-2-pyrrolidone (19.0 mL) was added sodium t-butoxide (2.38 g, 24.76 mmol), and the mixture was stirred at room temperature for 1 hr. A toluene solution (22.07 g) of bis(4-fluorophenyl)methylene chloride (4.54 g, 19.02 mmol) and potassium iodide (3.17 g, 19.10 mol) were added, and the mixture was stirred at 60° C. for 6 hrs. After completion of the reaction, 2M aqueous sodium hydroxide solution (45 mL) was added to the reaction mixture, and the mixture was stirred at 60° C. for 4 hrs. The reaction mixture was allowed to cool to room temperature and partitioned. The aqueous layer was adjusted to pH 7.0 with concentrated hydrochloric acid (4.4 mL). Ethyl acetate (30 mL) was added, and then concentrated hydrochloric acid (6.9 mL) was added. The mixture was partitioned and the aqueous layer was extracted with, ethyl acetate (6 mL). The organic layers were combined, and the content of the title compound was examined by HPLC to find 5.914 g thereof contained in the organic layer. The organic layer was successively washed with 2M hydrochloric acid (9 mL, three times) and saturated brine (4.5 mL), and concentrated at 40° C. to about ¼ in volume. The organic layer was cooled to allow crystal precipitation. After cooling to 0° C., the crystals were collected by filtration to give wet crystals. The powder X-ray (Cu—Kα ray) of the wet crystals showed characteristic peaks at 12.8°, 17.6°, 19.2° and 24.3°, as shown in FIG. 4.

1. stirringthe mixture was stirred at 60° C. for 6 hrs
2. additionwas added to the reaction mixture
3. stirringthe mixture was stirred at 60° C. for 4 hrs
4. temperatureto cool to room temperature
5. custompartitioned
6. additionEthyl acetate (30 mL) was added
7. additionconcentrated hydrochloric acid (6.9 mL) was added
8. customThe mixture was partitioned
9. extractionthe aqueous layer was extracted with, ethyl acetate (6 mL)
10. washThe organic layer was successively washed with 2M hydrochloric acid (9 mL, three times) and saturated brine (4.5 mL)
11. concentrationconcentrated at 40° C. to about ¼ in volume
12. temperatureThe organic layer was cooled
13. customcrystal precipitation
14. temperatureAfter cooling to 0° C.
15. filtrationthe crystals were collected by filtration
16. customto give wet crystals
17. customat 12.8°
18. custom17.6°, 19.2° and 24.3°