Hydrochloric Acid → Methyl 4-oxooxolane-3-carboxylate

HRID 732305Notes

Reaction equation

HRID 732305 reaction equation
[H-].[Na+].[C:3]([O:7][CH3:8])(=O)[CH2:4][OH:5].[C:9]([O:13][CH3:14])(=[O:12])[CH:10]=C.Cl>CCOCC.C(OCC)(=O)C.CCCCCC>[CH3:14][O:13][C:9]([CH:10]1[C:4](=[O:5])[CH2:3][O:7][CH2:8]1)=[O:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7294Methyl AcrylateHCID 24758Sodium hydrideHCID 66774Methyl Glycolate

Product 1

HCID 14666564Methyl 4-oxooxolane-3-carboxylateYield 54%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a suspension of NaH (6.66 g, 166.5 mmol) in ether (500 mL) add methyl glycolate (15.0 g, 166.5 mmol) drop wise. Stir the reaction until evolution of H2 gas ceases. Concentrate and dissolve the solid in DMSO (300 mL). Cool the reaction to 0° C. and add methyl acrylate (16.6 mL, 183.17 mmol) drop wise. Warm the reaction to room temperature and stir overnight. Acidify the reaction with 10% HCl and extract with ether (3×). Combine organic extracts and wash with brine. Dry the organic solution (Na2SO4), filter, and concentrate in vacuo. Purify by flash chromatography (250 g SiO2, 40 mL/min, 0-50% ethyl acetate/hexane for 20 minutes and then 50% ethyl acetate/hexane for 13 minutes) to yield 4-oxo-tetrahydro-furan-3-carboxylic acid methyl ester 4a (12.9 g, 89.2 mmol, 54%) as a colorless oil. 1H NMR (δ, 400 MHz, CDCl3): 4.50 (dd, 1H, J=8.4, 9.6 Hz), 4.46 (dd, 1H, J=8.4, 9.6 Hz), 4.05 (d, 1H, J=16.8 Hz), 3.79, (s, 3H), 3.97 (d, 1H, J=16.8, Hz), 3.54 (t, 1H, J=8.4 Hz). MS calcd. 144; found (EI) 144.

Workup

  1. customthe reaction until evolution of H2 gas ceases
  2. concentrationConcentrate
  3. dissolutiondissolve the solid in DMSO (300 mL)
  4. temperatureCool
  5. customthe reaction to 0° C.
  6. temperatureWarm
  7. customthe reaction to room temperature
  8. stirringstir overnight
  9. extractionextract with ether (3×)
  10. washCombine organic extracts and wash with brine
  11. dry with materialDry the organic solution (Na2SO4)
  12. filtrationfilter
  13. concentrationconcentrate in vacuo
  14. customPurify by flash chromatography (250 g SiO2, 40 mL/min, 0-50% ethyl acetate/hexane for 20 minutes

Sources & evidence

ORD record
ord-509b8eaf7e57498ba508248f69072637
Source dataset
uspto-grants-2009_09
Patent number
US07585985B2

Reaction notes

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