Dimethylformamide → 4-Benzyloxy-3-methoxy-toluene

HRID 1835407Notes

Reaction equation

HRID 1835407 reaction equation
CN(C)C=O.[CH3:6][O:7][C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[CH:10][C:9]=1[OH:15].[H-].[Na+].[CH2:18](Br)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCC)(=O)C.O>[CH2:18]([O:15][C:9]1[CH:10]=[CH:11][C:12]([CH3:14])=[CH:13][C:8]=1[O:7][CH3:6])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 6228Dimethylformamide3×HCID 71442-Methoxy-4-MethylphenolHCID 7498Benzyl BromideHCID 24758Sodium hydride

Product 1

HCID 50675084-Benzyloxy-3-methoxy-tolueneYield 99.8%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

A dimethylformamide (15 ml) solution of 2-methoxy-4-methylphenol (6.91 g) was dropwise added to a dimethylformamide (20 ml) suspension of sodium hydride (2.4 g) under cooling with ice, followed by stirring for 30 minutes. A dimethylformamide (15 ml) solution of benzyl bromide (9.41 g) was dropwise added thereto, and tetrabutylammonium bromide in a catalytic amount was added thereto, followed by stirring at the same temperature for 30 minutes. The temperature was raised to room temperature and stirring was further carried out for one night. The reaction solution was poured into water (250 ml), and extraction with ethyl acetate (100 ml) was carried out three times. The ethyl acetate phase was washed with water (100 ml) three times and then washed with an aqueous sodium chloride solution (100 ml). After drying over magnesium sulfate, the solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography (hexane-ethyl acetate) to obtain 11.4 g of 4-benzyloxy-3-methoxytoluene (m.p. 38-39° C.) quantitatively, and its structure was confirmed by nuclear magnetic resonance spectrum.

Workup

  1. temperatureunder cooling with ice
  2. stirringby stirring at the same temperature for 30 minutes
  3. stirringstirring
  4. waitwas further carried out for one night
  5. washThe ethyl acetate phase was washed with water (100 ml) three times
  6. washwashed with an aqueous sodium chloride solution (100 ml)
  7. dry with materialAfter drying over magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. customthe residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-08acecfe659a4b6b99ad1318fd1957f4
Source dataset
uspto-grants-2004_08
Patent number
US06770662B2

Reaction notes

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