Diethyl methylmalonate → Diethyl 2-methyl-2-(4-pyridylmethyl)malonate

HRID 18386

Reaction equation

HRID 18386 reaction equation
[H-].[Na+].[CH3:3][CH:4]([C:10]([O:12][CH2:13][CH3:14])=[O:11])[C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:16]1[CH:21]=[CH:20][N:19]=[C:18](CCl)[CH:17]=1.[C:24](=O)([O-])O.[Na+]>CN(C)C=O>[CH3:3][C:4]([CH2:24][C:16]1[CH:17]=[CH:18][N:19]=[CH:20][CH:21]=1)([C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

6

Reactant 4

HCID 11857Diethyl methylmalonateHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 130529014-Chloro-2-(chloromethyl)pyridine

Product 1

HCID 12136633Diethyl 2-methyl-2-(4-pyridylmethyl)malonate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

N,N-Dimethylformamide (143 ml) was added to sodium hydride (5.36 g, 134 mmol) under a nitrogen atmosphere, and the mixture was stirred under ice-cooling. A solution of diethyl methylmalonate (11.7 g, 67.1 mmol) in N,N-dimethylformamide (40 ml) was added dropwise to the mixture over five minutes, after 10 minutes, 4-chloropicolyl hydrochloride (10.0 g, 61.0 mmol) was added thereto little by little over five minutes, and the temperature was raised to room temperature. After one hour, a saturated aqueous sodium hydrogencarbonate solution (500 ml) was added to the reaction mixture, and the whole was extracted with diethyl ether (400 ml). The organic layer was washed with water (100 ml) and saturated brine (50 ml) successively, dried over magnesium sulfate and concentrated under reduced pressure to give diethyl 2-methyl-2-(4-pyridylmethyl)malonate (17.2 g, quantitatively, containing sodium hydride oil) as a brown oily matter.

Workup

  1. temperaturecooling
  2. waitAfter one hour
  3. extractionthe whole was extracted with diethyl ether (400 ml)
  4. washThe organic layer was washed with water (100 ml) and saturated brine (50 ml) successively
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-6432125f3aa84159a01537069af106c9
Source dataset
uspto-grants-2010_06
Patent number
US07741346B2

Linked notes

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