4-Hydroxybenzaldehyde → 4-(2-Hydroxy-2-phenylethoxy)benzaldehyde

HRID 2274322Notes

Reaction equation

HRID 2274322 reaction equation
F[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:10][O:9]2)=[CH:4][CH:3]=1.[OH:11][C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=1.[OH-].[Na+]>C1(C)C=CC=CC=1>[OH:9][CH:8]([C:5]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1)[CH2:10][O:11][C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 1264-HydroxybenzaldehydeHCID 14798Sodium HydroxideHCID 40652302-(4-Fluorophenyl)oxirane

Product 1

HCID 608843814-(2-Hydroxy-2-phenylethoxy)benzaldehydeYield 14.1%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
78 °C

Procedure

To 2-(4-fluorophenyl)oxirane (6.50 g, 54.0 mmol) was added toluene (85 mL), 4-hydroxybenzaldehyde (9.89 g, 81.0 mmol), PEG4000 (polyethylene glycol, 1.15 g) and 1M NaOH (85 mL) and the stirring mixture was heated at 78° C. overnight. After cooling to RT the reaction mixture was extracted with EtOAc, and the organic phase was washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The resulting yellow oil was chromatographed on a medium silica gel column eluting with 0-10% EtOAc/DCM. Fractions containing predominantly the higher Rf spot were combined and evaporated in vacuo to give 1.85 g (14%) of the title compound as a yellow oil. Fractions containing predominantly the lower Rf spot were combined and evaporated in vacuo to give 0.64 g of the regioisomer as a colorless, viscous oil. Mixed fractions were combined and rechromatographed eluting with 30% EtOAc/hexanes. Fractions containing the higher Rf material were combined and evaporated in vacuo to give an additional 2.64 g (20%) of the title compound as a colorless oil. Fractions containing the lower Rf material were combined and evaporated in vacuo to give an additional 1.82 g of the regioisomer as a colorless viscous oil.

Workup

  1. temperatureAfter cooling to RT the reaction mixture
  2. extractionwas extracted with EtOAc
  3. washthe organic phase was washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customThe resulting yellow oil was chromatographed on a medium silica gel column
  8. washeluting with 0-10% EtOAc/DCM
  9. additionFractions containing predominantly the higher Rf spot
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-7ddf85e24e1c482bbac46028e0d6e95c
Source dataset
uspto-grants-2015_09
Patent number
US09126959B2

Reaction notes

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