Diethyl Malonate → Diethyl 5H-Cyclopenta[b]pyridine-6,6(7H)-dicarboxylate

HRID 19733Notes

Reaction equation

HRID 19733 reaction equation
[Na].[C:2]([O:10][CH2:11][CH3:12])(=[O:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].Cl.Cl[CH2:15][C:16]1[C:21]([CH2:22]Cl)=[CH:20][CH:19]=[CH:18][N:17]=1>C(O)C>[CH2:11]([O:10][C:2]([C:3]1([C:4]([O:6][CH2:7][CH3:8])=[O:5])[CH2:15][C:16]2[N:17]=[CH:18][CH:19]=[CH:20][C:21]=2[CH2:22]1)=[O:9])[CH3:12]

Participants

5

Reactant 3

HCID 7761Diethyl MalonateHCID 5360545SodiumHCID 498578322,3-Bis(chloromethyl)pyridine hydrochloride

Product 1

HCID 21260369Diethyl 5H-Cyclopenta[b]pyridine-6,6(7H)-dicarboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

Sodium metal (0.345 g, 15.0 mmol) is dissolved in ethanol (20 ml) and diethyl malonate (0.713 g, 4.70 mmol) is added, followed by a suspension of 2,3-bis(chloromethyl)pyridine hydrochloride (Org. Process Res. Dev., 2002, 6, 938; 1.0 g, 4.70 mmol) in ethanol (15 ml) over 5 minutes. The reaction is heated to reflux for 5 hours, cooled to ambient temperature and filtered. The filtrate is evaporated, taken into water and extracted with ethyl acetate. The combined organic phases are washed with brine, dried (MgSO4) and evaporated. The crude product is purified by flash column chromatography (3:1-2:1 isohexanes-EtOAc gradient) to afford 5,7-dihydro-[1]pyrindine-6,6-dicarboxylic acid diethyl ester, MH+264.

Workup

  1. temperatureThe reaction is heated
  2. temperatureto reflux for 5 hours
  3. filtrationfiltered
  4. customThe filtrate is evaporated
  5. extractionextracted with ethyl acetate
  6. washThe combined organic phases are washed with brine
  7. dry with materialdried (MgSO4)
  8. customevaporated
  9. customThe crude product is purified by flash column chromatography (3:1-2:1 isohexanes-EtOAc gradient)

Sources & evidence

ORD record
ord-2fbe8299d8a94d909354b35d447df8ca
Source dataset
uspto-grants-2010_06
Patent number
US07745462B2

Reaction notes

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