تفاعل #64562

معادلة التفاعل

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

المردود 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

المردود 40.0%

المذيبات

H2O

DMF

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىThe cooled reaction mixture
2. 2
   استخلاصextracted twice with ethyl acetate
3. 3
   غسيلThe combined organic phase was washed with H2O and brine
4. 4
   تجفيفdried over Na2SO4
5. 5
   تركيزThe filtered solution was concentrated
6. 6
   أخرىchromatographed on 250 cc of silica gel
7. 7
   غسيلgradient elution with 6:1 to 5:1 hexane-EtOAc
8. 8
   أخرىwas recovered by further elution with 95:5 CH2Cl2

الإجراء التجريبي

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)+ .

المصدر