Diethyl isopropylidenemalonate → 2-(1-Cyclopropyl-1-methylethyl)malonic acid diethyl ester

HRID 1927655Notes

Reaction equation

HRID 1927655 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[C:6](=[C:9]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH3:8])[CH3:7]>C1COCC1.[Cu]I>[CH2:13]([O:12][C:10](=[O:11])[CH:9]([C:6]([CH:1]1[CH2:3][CH2:2]1)([CH3:7])[CH3:8])[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH3:14]

Participants

5

Reactant 2

HCID 81255Diethyl isopropylidenemalonateHCID 178418630HCID 178418630, compound

Product 1

HCID 672971112-(1-Cyclopropyl-1-methylethyl)malonic acid diethyl ester

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-50 °C

Procedure

To a suspension of copper(I) iodide (7.61 g, 40.0 mmol) in THF (50 mL) at −50° C. was added cyclopropylmagnesium bromide (160 mL, 80.0 mmol, 0.5 M in THF) under nitrogen. After stirring for 15 minutes, the suspension was allowed to warm up and stirred at rt for 20 min before cooling back to −50° C. A solution of diethyl isopropylidenemalonate (4.0 g, 20.0 mmol) in THF (50 mL) was added, and the reaction was allowed to warm to rt over 3 h. The reaction mixture was then quenched with saturated sodium bicarbonate (200 mL), and filtered through Celite. The filtrate was extracted with ethyl acetate (3×250 mL). The combined extracts were dried over sodium sulfate and concentrated, and the resulting residue was purified by silica gel chromatography eluting with diethyl ether/hexanes (1:10) to afford 2-(1-cyclopropyl-1-methylethyl)malonic acid diethyl ester.

Workup

  1. temperatureto warm up
  2. stirringstirred at rt for 20 min
  3. temperatureto warm to rt over 3 h
  4. customThe reaction mixture was then quenched with saturated sodium bicarbonate (200 mL)
  5. filtrationfiltered through Celite
  6. extractionThe filtrate was extracted with ethyl acetate (3×250 mL)
  7. dry with materialThe combined extracts were dried over sodium sulfate
  8. concentrationconcentrated
  9. customthe resulting residue was purified by silica gel chromatography
  10. washeluting with diethyl ether/hexanes (1:10)

Sources & evidence

ORD record
ord-a05f3f48d05f47d992c7bee4b686ac16
Source dataset
uspto-grants-2012_05
Patent number
US08183275B2

Reaction notes

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