Diethyl Malonate → HCID 11564752, compound

HRID 1530692Notes

Reaction equation

HRID 1530692 reaction equation
C(OCC)(=O)CC(OCC)=O.[H-].[Na+].C1(CBr)CC1.[CH2:19]([O:21][C:22](=[O:33])[CH:23]([CH2:29][CH2:30][CH:31]=[CH2:32])[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:20]>C1COCC1>[CH2:19]([O:21][C:22](=[O:33])[CH:23]([CH2:29][CH:30]1[CH2:32][CH2:31]1)[C:24]([O:26][CH2:27][CH3:28])=[O:25])[CH3:20]

Participants

6

Reactant 4

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 594682HCID 594682, compound

Product 1

HCID 11564752HCID 11564752, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice-cooled solution of diethyl malonate (3.0 g, 18.7 mmol) in THF (30 mL) was added, portionwise over 15 min, sodium hydride (0.824 g, 60% in oil, 20.6 mmol). The mixture was stirred at RT for 30 min, and then cooled in an ice bath. Cyclopropylmethyl bromide (2.36 mL, 24.3 mmol) was added and the reaction mixture stirred at RT for 1 h and then refluxed for 6 h. The cooled mixture was concentrated in vacuo, the residue was partitioned between diethyl ether and dilute aqueous NH4Cl; and the aqueous phase was extracted with diethyl ether. The combined organic phases were washed with brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% EtOAc in cyclohexane) affording a mixture of the title compound and 2-but-3-enylmalonic acid diethyl ester (3.24 g, 10:1 ratio respectively). This mixture was dissolved in DCM (150 mL) and a solution of mCPBA (0.77 g, 4.46 mmol) in DCM (5 mL) added. The reaction mixture was stirred at RT for 16 h, and then washed with a saturated solution of NaHCO3, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% EtOAc in cyclohexane) affording the title compound as a colourless oil (2.68 g, 67%). 1H NMR (CDCl3, 300 MHz): δ 4.20 (4H, q, J=7.1 Hz), 3.44 (1H, t, J=7.5 Hz), 1.81 (2H, t, J=7.3 Hz), 1.27 (6H, t, J=7.1 Hz), 0.80-0.67 (1H, m), 0.48-0.42 (2H, m), 0.12-0.07 (2H, m).

Workup

  1. additionwas added, portionwise over 15 min
  2. temperaturecooled in an ice bath
  3. stirringthe reaction mixture stirred at RT for 1 h
  4. temperaturerefluxed for 6 h
  5. concentrationThe cooled mixture was concentrated in vacuo
  6. customthe residue was partitioned between diethyl ether and dilute aqueous NH4Cl
  7. extractionand the aqueous phase was extracted with diethyl ether
  8. washThe combined organic phases were washed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customThe resulting residue was purified by column chromatography (Si-PCC, gradient 2-8% EtOAc in cyclohexane)
  12. customaffording

Sources & evidence

ORD record
ord-101fb2a15ed14a71b1212e3828efca0b
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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