Toluene → (2,4-Difluorophenyl)(3-methoxyphenyl)methanone

HRID 852077Notes

Reaction equation

HRID 852077 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=1)[OH:10].C1(C)C=CC=CC=1.C(OCC)(=O)C>CCCCCCC.[O-2].[Mn+2]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH3:18])[CH:12]=1)=[O:10]

Participants

6

Reactant 3

HCID 1140TolueneHCID 8857Ethyl AcetateHCID 17906348(2,4-Difluoro-phenyl)-(3-methoxy-phenyl)-methanol2×

Product 1

HCID 17906337(2,4-Difluorophenyl)(3-methoxyphenyl)methanoneYield 58.3%

Reagents, catalysts & solvents 2

HCID 160959Manganese oxideCatalystHCID 8900HeptaneSolvent

Procedure

Combine (2,4-difluoro-phenyl)-(3-methoxy-phenyl)-methanol (Compound 7) (89.2 g, 357 mmol), manganese oxide (96 g, 1.1 mol), and toluene (500 mL) and heat to reflux, under a nitrogen atmosphere for 2 hours. TLC (30% ethyl acetate in heptane) shows that the reaction is complete. Filter reaction mixture through celite® and concentrate. Purify by column chromatography using a graded solvent mixture of 10% dichloromethane in heptane to 50% dichloromethane in heptane to give an oil. Cool overnight to solidify, and triturate with pentane to give the title compound as a white solid (51.7 g, 58% Yield). NMR is consistent with the final, desired compound. mp=50° C.-52° C.

Workup

  1. temperatureto reflux, under a nitrogen atmosphere for 2 hours
  2. filtrationFilter
  3. customreaction mixture through celite®
  4. concentrationconcentrate
  5. customPurify by column chromatography
  6. additiona graded solvent mixture of 10% dichloromethane in heptane to 50% dichloromethane in heptane
  7. customto give an oil
  8. temperatureCool overnight
  9. customtriturate with pentane

Sources & evidence

ORD record
ord-475c77ecadc340ac938dd0bb3f4712d3
Source dataset
uspto-grants-2007_08
Patent number
US07253165B2

Reaction notes

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