反应详情

温度

80 °C

A mixture of 1-(4-fluorobenzyl)piperazin-2-one (10.0 g, 48.0 mmol) and diethyl ethoxymethylenemalonate (10.9 g, 50.4 mmol) in toluene (250 mL) was heated in a sealed tube at 80° C. for 4 hours. The resultant mixture was concentrated under vacuum. The residue was dissolved in anhydrous DMF (350 mL), cooled to 0° C. under an atmosphere of nitrogen, and treated with a solution of lithium bis(trimethylsilyl)amide in THF (1 M, 57.4 mL, 57.4 mmol). The reaction mixture was stirred at room temperature overnight and concentrated under vacuum. The residue was partitioned between ethyl acetate and dilute aqueous HCl. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was triturated with diethyl ether, and the solid precipitated was filtered to provide the titled compound.

1. concentrationThe resultant mixture was concentrated under vacuum
2. dissolutionThe residue was dissolved in anhydrous DMF (350 mL)
3. temperaturecooled to 0° C. under an atmosphere of nitrogen
4. concentrationconcentrated under vacuum
5. customThe residue was partitioned between ethyl acetate and dilute aqueous HCl
6. extractionThe organic extract
7. washwas washed with brine
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under vacuum
11. customThe residue was triturated with diethyl ether
12. customthe solid precipitated
13. filtrationwas filtered