反应详情

To a solution (1.25 M) of diethyl acetamidomalonate (13.33 g, 61.8 mmol) in N-methyl-2-pyrrolidone (40 mL) was added potassium t-butoxide (7.20 g, 64.3 mmol), and the mixture was stirred at room temperature for 1 hour. Diphenylmethylene chloride (10.0 g, 49.3 mmol) and potassium iodide (4.10 g, 24.7 mol) were added, and the mixture was stirred at 70° C. for 6 hours. After completion of the reaction, 2M aqueous sodium hydroxide solution (45 mL) was added to the reaction mixture, and the mixture was stirred for 5 hours at 60° C. After cooling to room temperature, the mixture was partitioned. The aqueous layer was adjusted to pH 7.0 with concentrated hydrochloric acid (4.4 mL), ethyl acetate (30 mL) and then concentrated hydrochloric acid (6.9 mL) were added, and the aqueous layer was extracted. The aqueous layer was further extracted with ethyl acetate (40 mL). The organic layers were combined, washed 3 times with 2M hydrochloric acid (20 mL), washed with saturated brine (10 mL), and concentrated. Toluene (30 mL) was added to the concentrate, and the mixture was concentrated at 50° C. Toluene (30 mL) was further added, and the mixture was stirred for 30 minutes. The mixture was cooled to 0° C. over 5 hours to allow precipitation of white crystals. The crystals were collected by filtration and dried under reduced pressure to give the title compound (11.69 g). The powder X-ray (Cu—Kα ray) of the dry crystals showed characteristic peaks at 5.8°, 11.5°, 21.6°, 23.2°, and 28.7°.

1. stirringthe mixture was stirred at 70° C. for 6 hours
2. additionwas added to the reaction mixture
3. stirringthe mixture was stirred for 5 hours at 60° C
4. temperatureAfter cooling to room temperature
5. customthe mixture was partitioned
6. additionconcentrated hydrochloric acid (6.9 mL) were added
7. extractionthe aqueous layer was extracted
8. extractionThe aqueous layer was further extracted with ethyl acetate (40 mL)
9. washwashed 3 times with 2M hydrochloric acid (20 mL)
10. washwashed with saturated brine (10 mL)
11. concentrationconcentrated
12. additionToluene (30 mL) was added to the concentrate
13. concentrationthe mixture was concentrated at 50° C
14. additionToluene (30 mL) was further added
15. stirringthe mixture was stirred for 30 minutes
16. temperatureThe mixture was cooled to 0° C. over 5 hours
17. customprecipitation of white crystals
18. filtrationThe crystals were collected by filtration
19. customdried under reduced pressure