Ethylene Glycol → [4-(1,3-Dioxolan-2-yl)phenyl]methanol

HRID 1428148Notes

Reaction equation

HRID 1428148 reaction equation
[CH:1]([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1)=[O:2].[CH2:13](O)CO.CC1C=CC(S(O)(=O)=O)=CC=1.O.[H-].COCCO[Al+]OCCOC.[Na+].[H-]>C1(C)C=CC=CC=1.CCOC(C)=O>[O:9]1[CH2:10][CH2:13][O:8][CH:7]1[C:6]1[CH:11]=[CH:12][C:3]([CH2:1][OH:2])=[CH:4][CH:5]=1

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 15294Methyl 4-FormylbenzoateHCID 521998p-Toluenesulfonic acid monohydrateHCID 21584525Sodium bis(2-methoxyethoxy)aluminiumhydride

Product 1

HCID 15192333[4-(1,3-Dioxolan-2-yl)phenyl]methanol

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
22 °C

Procedure

Methyl 4-formylbenzoate (4.92 g, 30.0 mmol) was dissolved in dry toluene (50.0 mL), successively treated with ethylene glycol (1.84 mL, 33.0 mmol) and p-TsOH.H2O (57.1 mg, 0.30 mmol), then heated to reflux under Dean-Stark conditions; acetal formation was complete within 1 h. The solution was then cooled to 22° C. and treated with sodium bis(2-methoxyethoxy)aluminum hydride (45.0 mmol; 12.7 mL of a 70.3 wt. % solution in toluene) at a rate of 0.5 mL/min using a syringe pump. CAUTION: vigorous gas evolution! Upon completion of the addition, the resulting solution was further cooled to 0° C., carefully treated with a saturated aqueous solution of K,Na-tartrate (100 ml), then vigorously stirred 1 h; steady formation of a clear solution was observed. The resulting biphase was then diluted with EtOAc (50 mL), with transfer to a conical funnel, and the layers separated. The aqueous layer was then washed with EtOAc (3×50 mL) and the combined EtOAc and toluene solutions dried over MgSO4, filtered and concentrated in vacuo to a colorless oil. The crude product was then purified by chromatography on silica (50×135 mm) using 1:1 pentane/EtOAc. The main product peak eluting 425-725 mL was collected, pooled and concentrated in vacuo to a colorless oil, which solidified in the freezer (4.50 g, 83.2% over two steps).

Workup

  1. temperatureheated
  2. temperatureto reflux under Dean-Stark conditions
  3. additionUpon completion of the addition
  4. temperaturethe resulting solution was further cooled to 0° C.
  5. customvigorously stirred 1 h
  6. customthe layers separated
  7. washThe aqueous layer was then washed with EtOAc (3×50 mL)
  8. dry with materialthe combined EtOAc and toluene solutions dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to a colorless oil
  11. customThe crude product was then purified by chromatography on silica (50×135 mm)
  12. washThe main product peak eluting 425-725 mL
  13. customwas collected
  14. concentrationconcentrated in vacuo to a colorless oil, which

Sources & evidence

ORD record
ord-fc5e9e34c8f74427906962c772761817
Source dataset
uspto-grants-2015_01
Patent number
US08936777B2

Reaction notes

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