반응 #51799

반응 방정식

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

용매

acetic acid

반응 조건

후처리

1. 1
   온도it was heated
2. 2
   온도to reflux for three hours
3. 3
   기타The 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
   추출was extracted with EtOAc
6. 6
   기타The 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
   기타The solvent was removed under reduced pressure
10. 10
    workup.DISSOLUTIONthe product was twice dissolved in ethanol
11. 11
    농축concentrated to a small volume under reduced pressure to azeotropically remove water
12. 12
    기타The title compound was recrystallized from ethanol and hexane (28.8 g)

실험 절차

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).

출처