Reaktion #51799

Reaktionsgleichung

ammonium acetate

1-(4-fluorophenyl)-2-(2-fluoropyridin-4-yl)ethane-1,2-dione 2-oxime

trimethylacetaldehyde

→

4-[2-tert-butyl-4-(4-fluorophenyl)-1-hydroxy-1H-imidazol-5-yl]pyridin-2(1H)-one

Lösungsmittel

acetic acid

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturit was heated
2. 2
   Temperaturto reflux for three hours
3. 3
   SonstigeThe acetic acid was removed under reduced pressure
4. 4
   workup.ADDITIONThe pH of the solution was adjusted to 8-10 by addition of solid ammonium hydroxide
5. 5
   Extraktionwas extracted with EtOAc
6. 6
   SonstigeThe solvent was removed under reduced pressure
7. 7
   workup.DISSOLUTIONthe crude product was dissolved in methanol with sufficient ethanol
8. 8
   workup.ADDITIONadded to effect dissolution
9. 9
   SonstigeThe solvent was removed under reduced pressure
10. 10
    workup.DISSOLUTIONthe product was twice dissolved in ethanol
11. 11
    Einengenconcentrated to a small volume under reduced pressure to azeotropically remove water
12. 12
    SonstigeThe title compound was recrystallized from ethanol and hexane (28.8 g)

Vorschrift

To a solution of 1-(4-fluorophenyl)-2-(2-fluoropyridin-4-yl)ethane-1,2-dione 2-oxime (47.3 g, 0.18 mol) in acetic acid (1 L) under nitrogen was added trimethylacetaldehyde (21.6 mL, 0.19 mol) followed by ammonium acetate (277.5 g, 3.6 mol) and then it was heated to reflux for three hours. The acetic acid was removed under reduced pressure and the remaining material was taken up in water. The pH of the solution was adjusted to 8-10 by addition of solid ammonium hydroxide and was extracted with EtOAc. The solvent was removed under reduced pressure and the crude product was dissolved in methanol with sufficient ethanol added to effect dissolution. The solvent was removed under reduced pressure; the product was twice dissolved in ethanol and concentrated to a small volume under reduced pressure to azeotropically remove water. The title compound was recrystallized from ethanol and hexane (28.8 g).

Quelle