Anisole → 2-[1'-Hydroxy-1'-(3-pyridyl)methyl]-4-tert-butylanisole

HRID 1389564Notes

Reaction equation

HRID 1389564 reaction equation
[Mg].I[C:3]1[CH:8]=[C:7]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:6]=[CH:5][C:4]=1[O:13][CH3:14].C1(OC)C=CC=CC=1.[CH:23](=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[N:26][CH:25]=1.[Cl-].[NH4+]>C(OCC)C>[OH:30][CH:23]([C:3]1[CH:8]=[C:7]([C:9]([CH3:12])([CH3:11])[CH3:10])[CH:6]=[CH:5][C:4]=1[O:13][CH3:14])[C:24]1[CH:25]=[N:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 5

HCID 7519Anisole2×HCID 103713-PyridinecarboxaldehydeHCID 25517Ammonium ChlorideHCID 5462224MagnesiumHCID 149144624-Tert-butyl-2-iodo-1-methoxybenzene

Product 1

HCID 202970232-[1'-Hydroxy-1'-(3-pyridyl)methyl]-4-tert-butylanisole

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent3×

Conditions

Temperature
0 °C

Procedure

270 mg of magnesium was suspended in 2 ml of anhydrous diethyl ether and 0.5 ml of a solution of 2-iodo-4-tert-butylanisole (prepared by dissolving 2.90 g of the anisole in 5 ml of diethyl ether), followed by warming the mixture to initiate the reaction. Upon addition of the remaining ethereal solution of the anisole, the mixture began to reflux. The mixture was refluxed for 30 minutes and then cooled to 0° C., and 1.03 ml of nicotinaldehyde dissolved in 5 ml of diethyl ether was added dropwise to the mixture. After stirring for one hour at 0° C., a saturated aqueous solution of ammonium chloride was added to the mixture which was then extracted with ethyl acetate. The ethyl acetate layer was washed successively with water and an aqueous sodium chloride solution, dried and concentrated. The residue was chromatographed on silica gel column using a mixed solvent of methylene chloride and ethyl acetate (1:1 by volume) as an eluting agent to give 1.76 g of the title compound having the following physical properties.

Workup

  1. temperatureby warming the mixture
  2. customthe reaction
  3. temperatureto reflux
  4. temperatureThe mixture was refluxed for 30 minutes
  5. additionwas added dropwise to the mixture
  6. extractionwas then extracted with ethyl acetate
  7. washThe ethyl acetate layer was washed successively with water
  8. dry with materialan aqueous sodium chloride solution, dried
  9. concentrationconcentrated
  10. customThe residue was chromatographed on silica gel column

Sources & evidence

ORD record
ord-4f46e26190b6467a89fa815e37221c03
Source dataset
uspto-grants-1981_01
Patent number
US04245099

Reaction notes

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