4-Fluorophenol → 4-methyl-1-(2-(4-fluorophenoxycarbonyl)-1H-indol-4-yl)piperazine

HRID 1383329ノート

反応式

HRID 1383329 の反応式
C(C1NC=CN=1)(C1NC=CN=1)=O.[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:21]=2[CH:22]=[C:23]([C:29]([OH:31])=[O:30])[NH:24]3)[CH2:16][CH2:15]1.[F:32][C:33]1[CH:38]=[CH:37][C:36](O)=[CH:35][CH:34]=1.[H-].[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:13][N:14]1[CH2:19][CH2:18][N:17]([C:20]2[CH:28]=[CH:27][CH:26]=[C:25]3[C:21]=2[CH:22]=[C:23]([C:29]([O:31][C:36]2[CH:37]=[CH:38][C:33]([F:32])=[CH:34][CH:35]=2)=[O:30])[NH:24]3)[CH2:16][CH2:15]1

参加物

7

反応物 4

HCID 97324-FluorophenolHCID 24758Sodium hydrideHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 211875904-(4-Methylpiperazin-1yl)indole-2-carboxylic acid

生成物 1

HCID 211875494-methyl-1-(2-(4-fluorophenoxycarbonyl)-1H-indol-4-yl)piperazine収率 25%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

A solution of carbonyl diimidazole (0.95 g, 5.86 mmol, 2.1 equivalents) and 4-(4-Methylpiperazin-1 yl)indole-2-carboxylic acid (0.710 g, 2.74 mmol) in anhydrous tetrahydrofuran (5 mL) was heated at 50° C. under nitrogen for 5 hours. The reaction was cooled to room temperature, and a preformed solution of 4-fluorophenol (2.90 g, 25.9 mmol, 9.4 equivalents) and sodium hydride (60% in oil, 1.17 g, 29.2 mmol, 10,7 equivalents) in anhydrous tetrahydrofuran (15 mL) was added rapidly. The resulting reaction solution was stirred at room temperature under nitrogen for 12 hours. Ethyl acetate (50 mL) was added to the reaction solution, and the resulting solution was extracted with a saturated solution of sodium hydrogen carbonate (2×25 mL). The organic layer was dried (magnesium sulfate), and evaporated under reduced pressure. The residue was chromatographed using silica gel (approximately 100 g) and elution with 20% methanol in ethyl acetate to afford crude 4-methyl-1-(2-(4-fluorophenoxycarbonyl)-1H-indol-4-yl)piperazine (0.225 g, 0.68 mmol crude, 25% crude).

後処理

  1. customThe resulting reaction solution
  2. extractionthe resulting solution was extracted with a saturated solution of sodium hydrogen carbonate (2×25 mL)
  3. dry with materialThe organic layer was dried (magnesium sulfate)
  4. customevaporated under reduced pressure
  5. customThe residue was chromatographed
  6. washsilica gel (approximately 100 g) and elution with 20% methanol in ethyl acetate

出典と根拠

ORDレコード
ord-227fd383f65e4baca48e62e2f937def3
出典データセット
uspto-grants-2001_07
特許番号
US06255306B1

反応ノート

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