Réaction #61857

Équation de réaction

2-acetoxy-3-methyl-1-(4′-fluoronaphth-1-yl)butan-1-one

hydrochloric acid

Cyanamide

2-hydroxy-3-methyl-1-(4′-fluoronaphth-1-yl)butan-1-one

1-hydroxy-3-methyl-l-(4′-fluoronaphth-1-yl)butan-2-one

→

title compound

Rendement 6.0%

2-amino-5-(4′-fluoronaphth-1-yl)-4-isopropyloxazole

Rendement 6.0%

Solvants

—

IMS

ethanol

Conditions de réaction

Traitement

1. 1
   Températureunder reflux for 4 hours
2. 2
   TempératureThe mixture was cooled
3. 3
   Autreevaporated in vacuo
4. 4
   Autrepartitioned between dichloromethane and brine
5. 5
   AutreThe organic layer was separated
6. 6
   Séchagedried with sodium sulphate
7. 7
   Filtrationfiltered
8. 8
   Autreevaporated in vacuo
9. 9
   AutreThe residue was purified by silica gel column chromatography in 66-100% dichloromethane in petroleum ether
10. 10
    Autreto afford
11. 11
    Températureunder reflux for 48 hours
12. 12
    TempératureAfter cooling the volatiles
13. 13
    Autrewere removed in vacuo
14. 14
    TempératureThe mixture was cooled
15. 15
    Autretriturated with chloroform (100 ml)
16. 16
    Filtrationfiltered
17. 17
    LavageThe filtrate was washed with water
18. 18
    Séchagedried with sodium sulphate
19. 19
    Filtrationfiltered
20. 20
    Autreevaporated in vacuo

Mode opératoire

A mixture of 2-acetoxy-3-methyl-1-(4′-fluoronaphth-1-yl)butan-1-one (4.8 g), IMS (100 ml) and hydrochloric acid (1M; 70 ml) were boiled under reflux for 4 hours. The mixture was cooled, evaporated in vacuo and partitioned between dichloromethane and brine. The organic layer was separated, dried with sodium sulphate, filtered and evaporated in vacuo. The residue was purified by silica gel column chromatography in 66-100% dichloromethane in petroleum ether to afford a mixture of 2-hydroxy-3-methyl-1-(4′-fluoronaphth-1-yl)butan-1-one and 1-hydroxy-3-methyl-l-(4′-fluoronaphth-1-yl)butan-2-one (3.2 g). Cyanamide (0.65 g) and anhydrous ethanol (10 ml) were added and the resulting mixture was boiled under reflux for 48 hours. After cooling the volatiles were removed in vacuo and the residue heated at 110° C. for a further 48 hours. The mixture was cooled, triturated with chloroform (100 ml) and filtered. The filtrate was washed with water, dried with sodium sulphate, filtered and evaporated in vacuo. The title compound (0.25 g; m.p. 141° C., softens from 125° C.) was obtained following silica gel column chromatography of the residue in 50% ethyl acetate in petroleum ether.

Source