Acetic Acid → Ethyl 2-(1-benzylpiperidin-4-ylidene)-2-cyanoacetate

HRID 844546Notes

Reaction equation

HRID 844546 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])#[N:16].C(O)(=O)C.C([O-])(=O)C.[NH4+]>C1(C)C=CC=CC=1.ClCCl.O>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[C:17]([C:15]#[N:16])[C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 7764Ethyl cyanoacetateHCID 192201-Benzyl-4-piperidoneHCID 517165Ammonium Acetate

Product 1

HCID 424752Ethyl 2-(1-benzylpiperidin-4-ylidene)-2-cyanoacetateYield 82%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 6344DichloromethaneSolvent

Procedure

N-Benzylpiperidin-4-one (25 g), ethyl cyanoacetate (16.4 g), glacial acetic acid (6 ml) and ammonium acetate (2.54 g) were heated together in toluene (200 ml), with removal of water using a Dean and Stark apparatus, for 90 minutes. The mixture was cooled, a further amount of toluene (100 ml) added and the solution washed sequentially with water (100 ml) and brine (100 ml) at which point a red oily product precipitated. The phases were separated and the oily product dissolved in dichloromethane. The toluene and dichloromethane solutions were combined and the solvents removed under reduced pressure to give a residue. The residue was dissolved in dichloromethane and washed sequentially with water and saturated aqueous sodium hydrogen carbonate solution before removal of the solvent under reduced pressure. The crude product was chromatographed on silica gel eluting with 98:2, by volume, dichloromethane:methanol to give the title compound (30.8 g) as an oil.

Workup

  1. temperatureThe mixture was cooled
  2. washthe solution washed sequentially with water (100 ml) and brine (100 ml) at which point a red oily product
  3. customprecipitated
  4. customThe phases were separated
  5. dissolutionthe oily product dissolved in dichloromethane
  6. customthe solvents removed under reduced pressure
  7. customto give a residue
  8. washwashed sequentially with water and saturated aqueous sodium hydrogen carbonate solution before removal of the solvent under reduced pressure
  9. customThe crude product was chromatographed on silica gel eluting with 98:2, by volume, dichloromethane

Sources & evidence

ORD record
ord-aad7a9984e534554b7e3c23d53a07ff2
Source dataset
uspto-grants-2002_04
Patent number
US06380396B1

Reaction notes

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