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

HRID 1383329Notes

Reaction equation

HRID 1383329 reaction equation
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

Participants

7

Reactant 4

HCID 97324-FluorophenolHCID 24758Sodium hydrideHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 21187590HCID 21187590, compound

Product 1

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

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-227fd383f65e4baca48e62e2f937def3
Source dataset
uspto-grants-2001_07
Patent number
US06255306B1

Reaction notes

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