4-Methoxyphenol → 4-(4-Methoxy-phenoxy)-3,5-dimethyl-nitrobenzene

HRID 2086151Notes

Reaction equation

HRID 2086151 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.Cl[C:11]1[C:16]([CH3:17])=[CH:15][C:14]([N+:18]([O-:20])=[O:19])=[CH:13][C:12]=1[CH3:21].C(=O)([O-])[O-].[K+].[K+]>CN1CCCC1=O.O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([O:9][C:11]2[C:12]([CH3:21])=[CH:13][C:14]([N+:18]([O-:20])=[O:19])=[CH:15][C:16]=2[CH3:17])=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 90154-MethoxyphenolHCID 11430Potassium CarbonateHCID 99205692-Chloro-1,3-dimethyl-5-nitrobenzene

Product 1

HCID 100846724-(4-Methoxy-phenoxy)-3,5-dimethyl-nitrobenzeneYield 6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
125 °C

Procedure

To a solution of 4-methoxyphenol (6.70 g, 53.9 mmol) and 4-chloro-3,5-dimethyl nitrobenzene (10 g, 53.9 mmol) in N-methylpyrrolidinone (50 mL) at room temperature was added potassium carbonate (8.19 g, 59.3 mmol). The reaction mixture was heated to 125° C. and stirred for 20 hours. The solution was cooled to room temperature, diluted with water (500 mL), and extracted with methylene chloride (3 times 300 mL). The combined organic extracts were washed with potassium hydroxide (0.1N, 3 times 500 mL), water (500 mL), brine (500 mL), dried (Na2SO4), filtered, and concentrated. The residue was dissolved in a mixture of ether (20 mL) and petroleum ether (30 mL) and the title compound was crystalized as a brown solid (6.84 g). The mother liquor was concentrated and purified by column chromatography (20% methylene chloride in hexane to 27.5% methylene chloride in hexane) to give an additional product (0.88 g) and the unreacted starting material (3.4 g). 1H NMR (400 MHz, CDCl3) δ7.97 (s, 2H), 6.78 (d, 2H), 6.64 (d, 2H), 3.74 (s, 3H), 2.18 (s, 6H).

Workup

  1. temperatureThe solution was cooled to room temperature
  2. extractionextracted with methylene chloride (3 times 300 mL)
  3. washThe combined organic extracts were washed with potassium hydroxide (0.1N, 3 times 500 mL), water (500 mL), brine (500 mL)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in a mixture of ether (20 mL) and petroleum ether (30 mL)
  8. customthe title compound was crystalized as a brown solid (6.84 g)
  9. concentrationThe mother liquor was concentrated
  10. custompurified by column chromatography (20% methylene chloride in hexane to 27.5% methylene chloride in hexane)

Sources & evidence

ORD record
ord-da2f41f2b4834a9f9260f4b7ad07e9a3
Source dataset
uspto-grants-2004_04
Patent number
US06723744B2

Reaction notes

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