Reacción #64562

Ecuación de reacción

5-n-butyl-2-[2-chloro-5-(methoxycarbonyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

5-n-Butyl-2-[2-chloro-5-(methoxycarbonyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

sodium hydride

4-bromo-2-fluorobenzyl bromide

hydrogen

→

title compound

Rendimiento 40.0%

4-(4-Bromo-2-fluorobenzyl)-5-n-butyl-2-[2-chloro-5-(methoxycarbonyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

Rendimiento 40.0%

Disolventes

H2O

DMF

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe cooled reaction mixture
2. 2
   Extracciónextracted twice with ethyl acetate
3. 3
   LavadoThe combined organic phase was washed with H2O and brine
4. 4
   Secadodried over Na2SO4
5. 5
   ConcentraciónThe filtered solution was concentrated
6. 6
   Otrochromatographed on 250 cc of silica gel
7. 7
   Lavadogradient elution with 6:1 to 5:1 hexane-EtOAc
8. 8
   Otrowas recovered by further elution with 95:5 CH2Cl2

Procedimiento

A mixture of 789 mg (2.55 mmole) of 5-n-butyl-2-[2-chloro-5-(methoxycarbonyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one (from Step C), 122.4 mg (3.06 mmole) of sodium hydride (60% in oil), and 2 mL of dry DMF was stirred at 50° C. for 2.5 hours, during which time hydrogen was evolved. A solution of 820 mg (3.06 mmole) of 4-bromo-2-fluorobenzyl bromide in DMF was added, and the mixture was stirred at 50° C. overnight. The cooled reaction mixture was diluted with H2O and extracted twice with ethyl acetate. The combined organic phase was washed with H2O and brine and then dried over Na2SO4. The filtered solution was concentrated, and the residue was flash chromatographed on 250 cc of silica gel packed in hexane (gradient elution with 6:1 to 5:1 hexane-EtOAc; some unreacted starting material was recovered by further elution with 95:5 CH2Cl2 --MeOH), yielding 503 mg (40%) of the title compound as an orange gum (TLC in 4:1 hexane-EtOAc), mass spectrum (FAB) m/e 496, 498 (M+1)+ .

Fuente