Methyl morpholine oxide → (2-Benzyloxy-6-methoxyphenyl)-(4-methoxyphenyl)methanol

HRID 554544Notes

Reaction equation

HRID 554544 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[C:10]=1[CH2:17][OH:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[N+]1([O-])[CH2:25][CH2:24][O:23][CH2:22]C1>ClCCl.[Ru]([O-])(=O)(=O)=O.C([N+](CCC)(CCC)CCC)CC>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[C:10]=1[CH:17]([C:2]1[CH:1]=[CH:25][C:24]([O:23][CH3:22])=[CH:4][CH:3]=1)[OH:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 82029Methyl morpholine oxideHCID 674586102-Benzyloxy-6-methoxybenzyl alcohol

Product 1

HCID 67459057(2-Benzyloxy-6-methoxyphenyl)-(4-methoxyphenyl)methanolYield 145%

Reagents, catalysts & solvents 2

HCID 178419074HCID 178419074, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

In a nitrogen stream, a solution of (2-benzyloxy-6-methoxyphenyl)-methanol (3.52 g, 14.41 mmol) and N-methylmorpholine N-oxide (NMO, 2.53 g, 21.61 mmol) in dichloromethane (14.5 mL) was cooled in a water bath, and tetra-n-propylammonium perruthenate (TPAP, 152 mg, 0.43 mmol) was added thereto. The reaction mixture was stirred for 20 minutes at the same temperature and at room temperature for 1.75 hours, and then subjected to Celite filtration and the solvent was distilled under reduced pressure. The obtained residue was treated by silica gel column chromatography [developing solution=ethyl acetate: n-hexane (1:3 to 1:2.5)]. The obtained compound was dissolved in THF and cooled in a water bath, and a solution of 4-methoxyphenylmagnesium bromide in THF (0.5 M, 30.3 mL) was added dropwise thereto in a nitrogen stream. The reaction mixture was stirred at room temperature for 1.25 hours, and then a saturated ammonium chloride aqueous solution was added thereto at room temperature and the mixture was extracted with ether. The organic layer was washed with a saturated ammonium chloride aqueous solution and dried (anhydrous sodium sulfate), and then the solvent was distilled under reduce pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:4 to 1:3.5)] to obtain the title compound (3.66 g, 72%).

Workup

  1. filtrationsubjected to Celite filtration
  2. distillationthe solvent was distilled under reduced pressure
  3. additionThe obtained residue was treated by silica gel column chromatography [developing solution=ethyl acetate: n-hexane (1:3 to 1:2.5)]
  4. dissolutionThe obtained compound was dissolved in THF
  5. temperaturecooled in a water bath
  6. additiona solution of 4-methoxyphenylmagnesium bromide in THF (0.5 M, 30.3 mL) was added dropwise
  7. stirringThe reaction mixture was stirred at room temperature for 1.25 hours
  8. additiona saturated ammonium chloride aqueous solution was added
  9. extractionat room temperature and the mixture was extracted with ether
  10. washThe organic layer was washed with a saturated ammonium chloride aqueous solution
  11. dry with materialdried (anhydrous sodium sulfate)
  12. distillationthe solvent was distilled
  13. customThe obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:4 to 1:3.5)]

Sources & evidence

ORD record
ord-3caa0c9d10f9441e83b20915501bd330
Source dataset
uspto-grants-2011_11
Patent number
US08048897B2

Reaction notes

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