Reaktion #657925

Reaktionsgleichung

4,4,4-trifluoro-N-[4-(2,2,2-trifluoroethoxy)phenyl]butanimidamide

diethyl malonate

sodium methoxide

→

title compound

6-hydroxy-3-[4-(2,2,2-trifluoroethoxy)phenyl]-2-(3,3,3-trifluoropropyl)pyrimidin-4(3H)-one

Lösungsmittel

2-methoxyethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwas heated
2. 2
   Temperaturunder reflux overnight
3. 3
   Einengenthe reaction mixture was concentrated under reduced pressure
4. 4
   workup.ADDITIONSimilarly, a mixture of 4,4,4-trifluoro-N-[4-(2,2,2-trifluoroethoxy)phenyl]butanimidamide (22.6 g), diethyl malonate (21.8 mL), sodium methoxide (11.7 g) and 2-methoxyethanol (400 mL)
5. 5
   Temperaturwas heated
6. 6
   Temperaturunder reflux overnight
7. 7
   Einengenthe reaction mixture was concentrated under reduced pressure
8. 8
   Sonstigepartitioned between diethyl ether and water
9. 9
   SonstigeThe aqueous layer was separated, to the organic layer
10. 10
    workup.ADDITIONwas added 1N hydrochloric acid
11. 11
    Extraktionthe mixture was extracted with ethyl acetate
12. 12
    WaschenThe extract was washed with saturated brine
13. 13
    Trocknendried over magnesium sulfate
14. 14
    Einengenconcentrated under reduced pressure
15. 15
    FiltrationThe precipitate was collected by filtration
16. 16
    Waschenwashed with diisopropyl ether
17. 17
    Sonstigedried

Vorschrift

A mixture of 4,4,4-trifluoro-N-[4-(2,2,2-trifluoroethoxy)phenyl]butanimidamide (20.9 g), diethyl malonate (20.2 mL), sodium methoxide (10.8 g) and 2-methoxyethanol (400 mL) was heated under reflux overnight, and the reaction mixture was concentrated under reduced pressure. Similarly, a mixture of 4,4,4-trifluoro-N-[4-(2,2,2-trifluoroethoxy)phenyl]butanimidamide (22.6 g), diethyl malonate (21.8 mL), sodium methoxide (11.7 g) and 2-methoxyethanol (400 mL) was heated under reflux overnight, and the reaction mixture was concentrated under reduced pressure. The obtained residues were combined, and partitioned between diethyl ether and water. The aqueous layer was separated, to the organic layer was added 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The obtained solid was suspended in diisopropyl ether. The precipitate was collected by filtration, washed with diisopropyl ether, and dried to give the title compound (41.6 g) as a solid.

Quelle