p-Toluenesulfonic acid → 1-Propanone, 1-(2,4-difluorophenyl)-2-[(tetrahydro-2H-pyran-2-YL)oxy]-,(2R)-

HRID 1654182Notes

Reaction equation

HRID 1654182 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:13])[CH:10]([OH:12])[CH3:11].C1(C)C=CC(S(O)(=O)=O)=CC=1.[O:25]1[CH:30]=[CH:29][CH2:28][CH2:27][CH2:26]1.C(=O)([O-])O.[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:13])[CH:10]([O:12][CH:26]1[CH2:27][CH2:28][CH2:29][CH2:30][O:25]1)[CH3:11]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 516892Sodium BicarbonateHCID 118301282',4'-Difluoro-2-hydroxypropiophenone

Product 1

HCID 108693411-Propanone, 1-(2,4-difluorophenyl)-2-[(tetrahydro-2H-pyran-2-YL)oxy]-,(2R)-Yield 97.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2',4'-Difluoro-2-hydroxypropiophenone (61 g) was dissolved in methylene chloride (500 ml), to which was added, under ice-cooling, p-toluene sulfonic acid.hydrate (1.0 g). To the mixture was added, under ice-cooling while stirring, 3,4-dihydro-2H-pyran (41.4 g) during 10 minutes. The mixture was stirred, under ice-cooling, for one hour, to which was added a 5% aqueous solution of sodium hydrogen carbonate (240 ml). The mixture was stirred for 10 minutes under ice-cooling. The methylene chloride layer was separated and dried over anhydrous magnesium sulfate, followed by distilling off the solvent. The residual oily product was purified by means of a silica gel column chromatography (hexane: ethyl acetate=5:1) to afford 2',4'-difluoro-2-(3,4,5,6-tetrahydro-2H-pyran-2-yloxy)propiophenone (86.5 g) as a pale yellow oily product.

Workup

  1. additionwas added, under ice-
  2. temperaturecooling
  3. additionTo the mixture was added, under ice-
  4. temperaturecooling
  5. stirringThe mixture was stirred, under ice-
  6. temperaturecooling, for one hour, to which
  7. stirringThe mixture was stirred for 10 minutes under ice-
  8. temperaturecooling
  9. customThe methylene chloride layer was separated
  10. dry with materialdried over anhydrous magnesium sulfate
  11. distillationby distilling off the solvent
  12. customThe residual oily product was purified by means of a silica gel column chromatography (hexane: ethyl acetate=5:1)

Sources & evidence

ORD record
ord-470f5ff8c17b447f8c8e2ffbda035a00
Source dataset
uspto-grants-1995_04
Patent number
US05405861

Reaction notes

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