反应详情

To a solution of diethyl acetamidomalonate (22.79 g, 105.4 mmol) in N-methyl-2-pyrrolidone (84 mL) was added 55% sodium hydride (4.58 g, 105.2 mmol), and the mixture was stirred at room temperature for 1 hr. Bis(4-fluorophenyl)methylene chloride (16.5 mL, 84.7 mmol) and potassium iodide (13.95 g, 84.0 mmol) were added, and the mixture was stirred at 50° C. for 5 hrs. After completion of the reaction, toluene (200 mL) and water (100 mL) were added to the reaction mixture, and the mixture was partitioned. The obtained organic layer was washed twice with water (100 mL) and concentrated. Ethanol (108 mL) and 2M aqueous sodium hydroxide solution (127 mL) were added to the concentrated solution, and the mixture was stirred at 90° C. for 2.5 hrs. The reaction mixture was allowed to cool to 25° C., toluene (200 mL) and water (50 mL) were added, and the mixture was partitioned. The aqueous layer was concentrated to a half volume, and isopropyl acetate (60 mL) and water (130 mL) were added. The mixture was adjusted to pH 1.1 with concentrated hydrochloric acid and partitioned. The organic layer was washed with water (200 mL), concentrated and dried under vacuum to give the title compound (28.24 g).

1. stirringthe mixture was stirred at 50° C. for 5 hrs
2. additionwere added to the reaction mixture
3. customthe mixture was partitioned
4. washThe obtained organic layer was washed twice with water (100 mL)
5. concentrationconcentrated
6. additionEthanol (108 mL) and 2M aqueous sodium hydroxide solution (127 mL) were added to the concentrated solution
7. stirringthe mixture was stirred at 90° C. for 2.5 hrs
8. temperatureto cool to 25° C.
9. additiontoluene (200 mL) and water (50 mL) were added
10. customthe mixture was partitioned
11. concentrationThe aqueous layer was concentrated to a half volume, and isopropyl acetate (60 mL) and water (130 mL)
12. additionwere added
13. custompartitioned
14. washThe organic layer was washed with water (200 mL)
15. concentrationconcentrated
16. customdried under vacuum