反应详情

To a solution (1.25 M) of diethyl acetamidomalonate (5.17 g, 23.80 mmol) in N-methyl-2-pyrrolidone (18.2 mL) was added potassium t-butoxide (2.77 g, 24.69 mmol), and the mixture was stirred at room temperature for 1 hr. A toluene solution (21.79 g) of bis(4-fluorophenyl)methylene chloride (4.54 g, 19.02 mmol) and potassium iodide (3.19 g, 19.10 mol) were added, and the mixture was stirred at 70° 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 5 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 5.678 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. Toluene (13.5 mL) was added to the concentrated solution, and the mixture was concentrated at 50° C. Toluene (13.5 mL) was added again, and the mixture was stirred for 30 min and cooled to 0° C. over 5 hrs, which resulted in the precipitation of white crystals. 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 17.1°, 17.6°, 18.8°, 20.7°, 21.8°, 22.0°, 22.7°, 23.1° and 25.4°, as shown in FIG. 2. The wet crystals were dried under reduced pressure to give the title compound (5.39 g) as dry crystals. The powder X-ray (Cu—Kα ray) of the dry crystals showed characteristic peaks at 17.1°, 21.8°, 22.0°, 22.7°, 23.1° and 25.4°, as shown in FIG. 3.

1. stirringthe mixture was stirred at 70° C. for 6 hrs
2. additionwas added to the reaction mixture
3. stirringthe mixture was stirred at 60° C. for 5 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
12. additionToluene (13.5 mL) was added to the concentrated solution
13. concentrationthe mixture was concentrated at 50° C
14. additionToluene (13.5 mL) was added again
15. stirringthe mixture was stirred for 30 min
16. temperaturecooled to 0° C. over 5 hrs
17. customwhich resulted in the precipitation of white crystals
18. filtrationThe crystals were collected by filtration
19. customto give wet crystals
20. customat 17.1°
21. custom17.6°, 18.8°, 20.7°, 21.8°, 22.0°, 22.7°, 23.1° and 25.4°
22. customThe wet crystals were dried under reduced pressure