Diethyl Malonate → Diethyl 3-(benzyloxy)cyclobutane-1,1-dicarboxylate

HRID 1497906Notes

Reaction equation

HRID 1497906 reaction equation
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Br[CH2:15][CH:16]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[CH2:17]Cl>O1CCOCC1>[CH2:20]([O:19][CH:16]1[CH2:17][C:4]([C:5]([O:7][CH2:8][CH3:9])=[O:6])([C:3]([O:11][CH2:12][CH3:13])=[O:10])[CH2:15]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydride2×HCID 3468282{[(1-Bromo-3-chloropropan-2-yl)oxy]methyl}benzene

Product 1

HCID 12815110Diethyl 3-(benzyloxy)cyclobutane-1,1-dicarboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a stirred suspension of sodium hydride (920 mg, 23 mmol, 60% in mineral oil) in dry dioxane (33 mL), was added diethyl malonate (3.5 mL, 23 mmol) dropwise over min. After the addition was complete, (((1-bromo-3-chloropropan-2-yl)oxy)methyl)benzene (157) (6.1 g, 23 mmol) was added over 20 minutes. The mixture was then heated at reflux for 24 hours. After cooling to room temperature, sodium hydride (920 mg, 23 mmol) in dioxane (2 mL) was added to the mixture and heating at reflux for another 48 hours. The solvent was partially removed under reduced pressure and the mixture was treated with water (50 mL). The mixture was extracted with ethyl acetate (3×30 mL), dried with magnesium sulfate and concentrated in vacuo. The crude product was purified by column chromatography using hexanes/ethyl acetate as eluent (25%) to yield diethyl 3-(benzyloxy)cyclobutane-1,1-dicarboxylate (158). 1H NMR (400 MHz, CD2Cl2) δ 7.39-7.30 (m, 5H), 4.4 (s, 2H), 4.23-4.13 (m, 5H), 2.83-2.78 (m, 2H), 2.55-2.49 (m, 2H), 1.32-1.25 (m, 6H). MS m/z 307.2 (M+1)+.

Workup

  1. additionAfter the addition
  2. temperatureThe mixture was then heated
  3. temperatureat reflux for 24 hours
  4. temperatureheating
  5. temperatureat reflux for another 48 hours
  6. customThe solvent was partially removed under reduced pressure
  7. additionthe mixture was treated with water (50 mL)
  8. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
  9. dry with materialdried with magnesium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-09e6ce864a124c04862f09a2dc73b9ff
Source dataset
uspto-grants-2015_12
Patent number
US09199981B2

Reaction notes

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