Hydrochloric Acid → 3-[2-(Benzyloxy)-2-oxoethylidene]cyclobutane-1-carboxylic acid

HRID 2040656Notes

Reaction equation

HRID 2040656 reaction equation
[CH2:1]([O:8][C:9](=[O:17])[CH2:10]P(OC)(OC)=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li+].[OH-].CC[O:22][C:23]([CH3:25])=[O:24].Cl.[CH2:27]1[CH2:31]OC[CH2:28]1>>[CH2:1]([O:8][C:9](=[O:17])[CH:10]=[C:27]1[CH2:31][CH:25]([C:23]([OH:22])=[O:24])[CH2:28]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 2773759Benzyl Dimethylphosphonoacetate

Product 1

HCID 677753443-[2-(Benzyloxy)-2-oxoethylidene]cyclobutane-1-carboxylic acidYield 39%

Procedure

A mixture of cyclobutaneone-3-carboxylic acid (5 g, 43.82 mmol), benzyl-2-(dimethoxyphosphoryl)acetate (13.58 g, 52.59 mmol), LiOH (4.20 g, 23.95 mmol) and 3 Å activated molecular sieves (25 g, powder form) in THF (250 ml) was heated to reflux under nitrogen for 4 h. The reaction was allowed to cool to RT and EtOAc (100 ml) followed by HCl (1N, 100 ml) were added. This mixture was filtered through celite. The phases were separated and the aqueous layer was extracted with EtOAc (4×50 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated to yield a colorless oil. Dry flash chromatography over SiO2, eluting with Hept:EtOAc from 7:3 to 1:1 gave the desired product as a colorless oil (5.2 g, 39%); MS (ESI+) for C14H14O4 m/z 269.05 [M+Na]+; MS (ESI−) for C14H14O4 m/z 245.15 [M−H]−; HPLC purity 81% (ret. time, 1.85 min); 1H NMR (250 MHz, CHLOROFORM-d) δH ppm 2.95-3.62 (5 H, m), 4.96-5.31 (2 H, m), 5.75 (1 H, t, J=2.21 Hz), 7.27-7.45 (5 H, m).

Workup

  1. temperaturewas heated
  2. temperatureto reflux under nitrogen for 4 h
  3. additionwere added
  4. filtrationThis mixture was filtered through celite
  5. customThe phases were separated
  6. extractionthe aqueous layer was extracted with EtOAc (4×50 ml)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield a colorless oil
  11. customDry flash chromatography over SiO2
  12. washeluting with Hept

Sources & evidence

ORD record
ord-85282be6ce844ec7875c4f89eb4732fc
Source dataset
uspto-grants-2013_11
Patent number
US08580762B2

Reaction notes

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