Reaktion #64562

Reaktionsgleichung

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

Ausbeute 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

Ausbeute 40.0%

Lösungsmittel

H2O

DMF

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe cooled reaction mixture
2. 2
   Extraktionextracted twice with ethyl acetate
3. 3
   WaschenThe combined organic phase was washed with H2O and brine
4. 4
   Trocknendried over Na2SO4
5. 5
   EinengenThe filtered solution was concentrated
6. 6
   Sonstigechromatographed on 250 cc of silica gel
7. 7
   Waschengradient elution with 6:1 to 5:1 hexane-EtOAc
8. 8
   Sonstigewas recovered by further elution with 95:5 CH2Cl2

Vorschrift

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)+ .

Quelle