反応 #64562

反応方程式

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

収率 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

収率 40.0%

溶媒

H2O

DMF

DMF

反応条件

後処理

1. 1
   その他The cooled reaction mixture
2. 2
   抽出extracted twice with ethyl acetate
3. 3
   洗浄The combined organic phase was washed with H2O and brine
4. 4
   乾燥dried over Na2SO4
5. 5
   濃縮The filtered solution was concentrated
6. 6
   その他chromatographed on 250 cc of silica gel
7. 7
   洗浄gradient elution with 6:1 to 5:1 hexane-EtOAc
8. 8
   その他was recovered by further elution with 95:5 CH2Cl2

実験手順

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)+ .

出典