Water → 1-(2-(P-NO2Phenoxy)ethyl)imidazole

HRID 2415294Notes

Reaction equation

HRID 2415294 reaction equation
[N:1]1([CH2:6][CH2:7][OH:8])[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].F[C:12]1[CH:17]=[CH:16][C:15]([N+:18]([O-:20])=[O:19])=[CH:14][CH:13]=1.O>CN(C)C=O>[N+:18]([C:15]1[CH:16]=[CH:17][C:12]([O:8][CH2:7][CH2:6][N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)=[CH:13][CH:14]=1)([O-:20])=[O:19]

Participants

6

Reactant 4

HCID 962WaterHCID 9590p-FluoronitrobenzeneHCID 24758Sodium hydrideHCID 74168N-(2-Hydroxyethyl)imidazole

Product 1

HCID 135691861-(2-(P-NO2Phenoxy)ethyl)imidazoleYield 42%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 2-imidazol-1-yl-ethanol (J. Med. Chem., 39(10), 1991, (1996)) (3.9 g, 35 mmol) in dimethylformamide (75 mL) at 15° C. was treated portionwise with 60% sodium hydride (0.84 g, 35 mmol) and stirred at room temperature for 30 minutes. The mixture was rechilled and 4-fluoro-1-nitrobenzene (4.93 g, 35 mmol) added dropwise. The mixture was stirred cold for 30 minutes and heated at 35-40° C. for 30 minutes. A little water was added and the volatiles were removed on a pump. The residue was diluted with water, extracted with dichloromethane, washed with brine, dried (Na2SO4) and evaporated. Chromatography on silica gel and eluting with methanol/triethyl-amine/dichloromethane (2:2:96) and crystallization of the purified product from dichloromethane/ether gave 3.4 g (42%) of 1-[2-(4-nitro-phenoxy)ethyl]-1H-imidazole as a colorless solid, mp 55-57° C. Mass spectrum (LR-APCI) MH+=234.

Workup

  1. stirringThe mixture was stirred cold for 30 minutes
  2. temperatureheated at 35-40° C. for 30 minutes
  3. customthe volatiles were removed on a pump
  4. additionThe residue was diluted with water
  5. extractionextracted with dichloromethane
  6. washwashed with brine
  7. dry with materialdried (Na2SO4)
  8. customevaporated
  9. washChromatography on silica gel and eluting with methanol/triethyl-amine/dichloromethane (2:2:96) and crystallization of the purified product from dichloromethane/ether

Sources & evidence

ORD record
ord-3d1944a056904d678876c24363ea825e
Source dataset
uspto-grants-2004_11
Patent number
US06818663B2

Reaction notes

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