Hydrochloric Acid → 4-hydroxy-5-methyl-5-phenyl-3-phenylmethoxy-2-(5H)-furanone

HRID 369136Notes

Reaction equation

HRID 369136 reaction equation
[C:1]([C:9]([O:11]CC)=O)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Mg]I.[CH2:17]([O:24][CH2:25][C:26](Cl)=[O:27])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[Li+].[CH3:30]C([N-]C(C)C)C.Cl>C1COCC1.CCOCC>[OH:11][C:9]1[C:1]([CH3:30])([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[O:8][C:26](=[O:27])[C:25]=1[O:24][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 15349Ethyl benzoylformateHCID 177085Benzyloxyacetyl chlorideHCID 2724682Lithium diisopropylamideHCID 178418373HCID 178418373, compound

Product 1

HCID 702488804-hydroxy-5-methyl-5-phenyl-3-phenylmethoxy-2-(5H)-furanoneYield 20%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a 2-necked flask flame dried under argon with septum and charged with a solution of 3.6 g (20 mmol) of ethyl benzoylformate in 50 mL of anhydrous THF at -30° C. was slowly added 7 mL (21 mmol) of a 3.0 M solution of methylmagnesium iodide. The reaction mixture was stirred at 0° C. for 45 minutes, then at room temperature for 30 minutes and again cooled to 0° C. Benzyloxyacetyl chloride (3.4 mL, 21 mmol) was added and the reaction mixture was stirred at room temperature for 1 hour, cooled to -78° C. and 33 mL of a 1.5M solution of LDA in THF was added with rapid stirring. The mixture was worked up after 1 hour by the addition of 100 mL of aqueous 10% HCl solution and 300 mL of ether. The layers were separated and the organic phase was washed with 50 mL aqueous 10% HCl solution, 30 mL of H2O, and extracted with 3×40 mL of saturated NaHCO3 solution. The bicarbonate extracts were combined and washed with 40 mL of ether, acidified to pH 1 with 10% aqueous HCl solution, and extracted with 2×80 mL of ether. The organic fractions were combined, washed with 25 mL of H2O, 25 mL of brine, dried (MgSO4), and concentrated leaving 1.2 g (20% yield) of 4-hydroxy-5-methyl-5-phenyl-3-phenylmethoxy-2-(5H)-furanone as a yellow oil.

Workup

  1. temperatureTo a 2-necked flask flame
  2. customdried under argon with septum
  3. waitat room temperature for 30 minutes
  4. temperatureagain cooled to 0° C
  5. stirringthe reaction mixture was stirred at room temperature for 1 hour
  6. temperaturecooled to -78° C.
  7. customThe layers were separated
  8. washthe organic phase was washed with 50 mL aqueous 10% HCl solution, 30 mL of H2O
  9. extractionextracted with 3×40 mL of saturated NaHCO3 solution
  10. washwashed with 40 mL of ether
  11. extractionextracted with 2×80 mL of ether
  12. washwashed with 25 mL of H2O, 25 mL of brine
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-b4a194244c0142ef91700ada38a51967
Source dataset
uspto-grants-2000_10
Patent number
US06136832

Reaction notes

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