Diethyl methylmalonate → Propanedioic acid, methyl[2-(2-thienyl)ethyl]-, diethyl ester

HRID 2086177Notes

Reaction equation

HRID 2086177 reaction equation
[H-].[Na+].[CH2:3]([O:5][C:6](=[O:14])[CH:7]([CH3:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:4].I[CH2:16][CH2:17][C:18]1[S:19][CH:20]=[CH:21][CH:22]=1>CN(C)C=O>[CH2:3]([O:5][C:6](=[O:14])[C:7]([CH2:16][CH2:17][C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)([CH3:13])[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:4]

Participants

5

Reactant 3

HCID 11857Diethyl methylmalonateHCID 24758Sodium hydrideHCID 152732602-(2-Iodoethyl)thiophene

Product 1

HCID 85759744Propanedioic acid, methyl[2-(2-thienyl)ethyl]-, diethyl esterYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (55%, 18.8 g, 0.43 mol) was suspended in dimethylformamide (200 ml), and methylmalonic acid diethylester (50.0 g, 0.29 mol) was slowly added thereto for 30 minutes in an ice bath, and then the reaction solution was stirred for 30 minutes. To the reaction solution was added 2-(2-iodoethyl)thiophene (75.2 g, 0.32 mol) dissolved in dimethylformamide (200 ml) under a nitrogen atmosphere for 15 minutes, and then the reaction mixture was stirred for 4 hours at room temperature. The reaction mixture was poured into ice-cold 10% hydrochloric acid (500 ml), and extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was concentrated under reduced pressure, and the residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=10:1-5:1) to afford the title compound (53.1 g, 65% yield) as a colorless oil.

Workup

  1. stirringthe reaction mixture was stirred for 4 hours at room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationThe solvent was concentrated under reduced pressure
  6. customthe residue was purified by flash chromatography on a silica gel column (elution solvent; hexane:ethyl acetate=10:1-5:1)

Sources & evidence

ORD record
ord-0a6e97684af3462d8a9daece8d9229a5
Source dataset
uspto-grants-2004_04
Patent number
US06723745B2

Reaction notes

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