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

HRID 36284

反応式

HRID 36284 の反応式
[CH2:1]([C:5]1[NH:6][C:7](=[O:21])[N:8]([C:10]2[CH:15]=[C:14]([C:16]([O:18][CH3:19])=[O:17])[CH:13]=[CH:12][C:11]=2[Cl:20])[N:9]=1)[CH2:2][CH2:3][CH3:4].[H-].[Na+].[H][H].[Br:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Br)=[C:29]([F:35])[CH:28]=1>CN(C=O)C.O>[Br:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31][N:6]2[C:5]([CH2:1][CH2:2][CH2:3][CH3:4])=[N:9][N:8]([C:10]3[CH:15]=[C:14]([C:16]([O:18][CH3:19])=[O:17])[CH:13]=[CH:12][C:11]=3[Cl:20])[C:7]2=[O:21])=[C:29]([F:35])[CH:28]=1

参加物

7

反応物 4

HCID 24758Sodium hydrideHCID 27336604-Bromo-2-fluorobenzyl bromideHCID 1357200825-n-Butyl-2-[2-chloro-5-(methoxycarbonyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-oneHCID 178418361HCID 178418361、化合物

生成物 1

HCID 100060494-(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%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
50 °C

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)+ .

後処理

  1. customThe cooled reaction mixture
  2. extractionextracted twice with ethyl acetate
  3. washThe combined organic phase was washed with H2O and brine
  4. dry with materialdried over Na2SO4
  5. concentrationThe filtered solution was concentrated
  6. customchromatographed on 250 cc of silica gel
  7. washgradient elution with 6:1 to 5:1 hexane-EtOAc
  8. customwas recovered by further elution with 95:5 CH2Cl2

出典と根拠

ORDレコード
ord-bea94300c7df438382147d599c77b1a9
出典データセット
uspto-grants-1995_05
特許番号
US05411980

関連ノート

読み込み中…