反应详情

温度

100 °C

A mixture of 1-methylpiperazin-2-one (183 g, 1.6 mol) and diethyl ethoxymethylenemalonate (346 g, 1.6 mol) in toluene (12 L) was heated at 100° C. overnight. The resultant mixture was concentrated under vacuum. The residue was dissolved in anhydrous THF (8 L), brought to reflux under an atmosphere of nitrogen, and treated with a solution of lithium bis(trimethylsilyl)amide in THF (1 M, 1.05 eq). The reaction mixture was allowed to cool to room temperature and concentrated under vacuum. The residue was partitioned between methylene chloride 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 ethyl acetate, cooled to −20° C., and the solid precipitated was filtered to provide the title compound.

1. concentrationThe resultant mixture was concentrated under vacuum
2. dissolutionThe residue was dissolved in anhydrous THF (8 L)
3. temperatureto reflux under an atmosphere of nitrogen
4. temperatureto cool to room temperature
5. concentrationconcentrated under vacuum
6. customThe residue was partitioned between methylene chloride and dilute aqueous HCl
7. extractionThe organic extract
8. washwas washed with brine
9. dry with materialdried over anhydrous magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated under vacuum
12. customThe residue was triturated with ethyl acetate
13. temperaturecooled to −20° C.
14. customthe solid precipitated
15. filtrationwas filtered