Reacción #61857

Ecuación de reacción

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

Rendimiento 6.0%

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

Rendimiento 6.0%

Disolventes

—

IMS

ethanol

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaunder reflux for 4 hours
2. 2
   TemperaturaThe mixture was cooled
3. 3
   Otroevaporated in vacuo
4. 4
   Otropartitioned between dichloromethane and brine
5. 5
   OtroThe organic layer was separated
6. 6
   Secadodried with sodium sulphate
7. 7
   Filtraciónfiltered
8. 8
   Otroevaporated in vacuo
9. 9
   OtroThe residue was purified by silica gel column chromatography in 66-100% dichloromethane in petroleum ether
10. 10
    Otroto afford
11. 11
    Temperaturaunder reflux for 48 hours
12. 12
    TemperaturaAfter cooling the volatiles
13. 13
    Otrowere removed in vacuo
14. 14
    TemperaturaThe mixture was cooled
15. 15
    Otrotriturated with chloroform (100 ml)
16. 16
    Filtraciónfiltered
17. 17
    LavadoThe filtrate was washed with water
18. 18
    Secadodried with sodium sulphate
19. 19
    Filtraciónfiltered
20. 20
    Otroevaporated in vacuo

Procedimiento

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.

Fuente