Diethyl Malonate → (Cyclopentylmethyl)propanedioic acid

HRID 1666941Notes

Reaction equation

HRID 1666941 reaction equation
[C:1]([O:9]CC)(=[O:8])[CH2:2][C:3]([O:5]CC)=[O:4].C[O-].[Na+].Br[CH2:16][CH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1.[OH-].[Na+]>O.CO>[CH:17]1([CH2:16][CH:2]([C:3]([OH:5])=[O:4])[C:1]([OH:9])=[O:8])[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 7761Diethyl MalonateHCID 14798Sodium HydroxideHCID 10942334Sodium MethoxideHCID 12723264(Bromomethyl)cyclopentane

Product 1

HCID 55250614(Cyclopentylmethyl)propanedioic acidYield 59%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

A solution of diethyl malonate (36.91 g, 230.4 mmol), anhydrous methanol (400 mL), and NaOMe (25% in methanol, 49.79 g, 230.4 mmol) is stirred at reflux for one hour under nitrogen. Bromomethyl-cyclopentane (31.31 g, 192.0 mmol) is added to the mixture, and stirred for an additional 3 hours. A solution of NaOH (23.04 g, 576.0 mmol) in water (400 mL) is added, and the mixture is stirred for an additional 1 hour at reflux. The mixture is cooled, diluted with water, and extracted with ether. The ether layer is discarded, and the aqueous layer is acidified with 1N HCl to pH=1. The aqueous layer is extracted with EtOAc. The EtOAc layers are combined, dried over Na2SO4, and concentrated. This gives 2-cyclopentylmethyl-malonic acid (21.0 g, 59% yield) as a white solid.

Workup

  1. temperatureat reflux for one hour under nitrogen
  2. stirringthe mixture is stirred for an additional 1 hour
  3. temperatureat reflux
  4. temperatureThe mixture is cooled
  5. extractionextracted with ether
  6. extractionThe aqueous layer is extracted with EtOAc
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-38d86fefef784c2ba60afdd9fee24131
Source dataset
uspto-grants-2011_10
Patent number
US08044199B2

Reaction notes

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