Dimethyl malonate → HCID 86584484, compound

HRID 341774Notes

Reaction equation

HRID 341774 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].[C:12]([O:16][C:17]([N:19]1[CH2:23][CH:22]=[C:21]([CH2:24]OC(=O)C)[CH2:20]1)=[O:18])([CH3:15])([CH3:14])[CH3:13]>C1COCC1.CCOCC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:6][O:5][C:3](=[O:4])[CH:2]([CH2:24][C:21]1[CH2:20][N:19]([C:17]([O:16][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:18])[CH2:23][CH:22]=1)[C:1]([O:8][CH3:9])=[O:7]

Participants

7

Reactant 3

HCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 53886620HCID 53886620, compound

Product 1

HCID 86584484HCID 86584484, compoundYield 77.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

5.28 g (40 mmol) dimethyl malonate were cautiously added to an ice-cooled suspension of 864 mg (36 mmol) sodium hydride in 80 ml THF. The resulting clear solution was added to a solution of 4.82 g (20 mmol) 3-acetoxymethyl-2,5-dihydro-pyrrole-1-carboxylic acid tert.-butylester and 462 mg (0.4 mmol) Pd(PPh3)4 in 40 ml THF and the mixture was heated to reflux for 20 h. The reaction mixture was cooled to room temperature, diluted with ether and quenched with sat. NH4Cl. The organic layer was washed with sat. NH4Cl and brine, dried over MgSO4 and evaporated. The residue was purified by flash chromatography (ethyl acetate/petrol ether 4:1 to 2:1) and bulb-to-bulb distilled to yield 4.86 g (77%) of 2(1-tert.-butoxycarbonyl-2,5-dihydro-1H-pyrrol-3 -yl-methyl)-malonic acid dimetylester as a colorless oil, b.p. 130° C./0.2 mbar.

Workup

  1. temperaturecooled
  2. temperaturethe mixture was heated
  3. temperatureto reflux for 20 h
  4. customquenched with sat. NH4Cl
  5. washThe organic layer was washed with sat. NH4Cl and brine
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customThe residue was purified by flash chromatography (ethyl acetate/petrol ether 4:1 to 2:1) and bulb-to-bulb
  9. distillationdistilled

Sources & evidence

ORD record
ord-6725785c782a4206ad23f7ec6f82b125
Source dataset
uspto-grants-1999_01
Patent number
US05856309

Reaction notes

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