Acetic Acid → TERT-BUTYL 4-(1-CYANO-2-ETHOXY-2-OXOETHYLIDENE)PIPERIDINE-1-CARBOXYLATE

HRID 1992057Notes

Reaction equation

HRID 1992057 reaction equation
O=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.[C:15]([CH2:17][C:18]([O:20][CH2:21][CH3:22])=[O:19])#[N:16].C([O-])(=O)C.[NH4+].C(O)(=O)C>C1C=CC=CC=1>[C:15]([C:17](=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1)[C:18]([O:20][CH2:21][CH3:22])=[O:19])#[N:16]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7764Ethyl cyanoacetateHCID 517165Ammonium AcetateHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 11551073TERT-BUTYL 4-(1-CYANO-2-ETHOXY-2-OXOETHYLIDENE)PIPERIDINE-1-CARBOXYLATE

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

A mixture of tert-butyl 4-oxo-1-piperidinecarboxylate (25.25 g, 127 mmol), ethyl cyanoacetate (13.8 ml, 130 mmol), ammonium acetate (2.73 g, 35.4 mmol), glacial acetic acid (6.3 ml) and benzene (250 ml) was heated for 4 hours at reflux under Dean Stark conditions. The reaction mixture was cooled to room temperature and washed successively with water, sodium bicarbonate solution and brine. Drying, filtration and evaporation of the organic phase provided tert-butyl 4-(1-cyano-2-ethoxy-2-oxoethylidene)piperidine-1-carboxylate as an oil that crystallized on standing (37 g, 99%). 1H NMR (400 MHz, CDCl3): δ 4.28 (q, 2H, J=7 Hz), 3.60 (br t, 2H, J=6 Hz), 3.54 (br t, 2H, J=6 Hz), 3.12 (t, 2H, J=6 Hz), 2.76 (t, 2H, J=6 Hz), 1.47 (s, 9H), and 1.35 (t, 3H, J=7 Hz). ES-LCMS m/z 293 (M−1).

Workup

  1. temperaturewas heated for 4 hours
  2. temperatureat reflux under Dean Stark conditions
  3. washwashed successively with water, sodium bicarbonate solution and brine
  4. customDrying
  5. filtrationfiltration and evaporation of the organic phase

Sources & evidence

ORD record
ord-2bcba03b9b5c4d91a83543a1f16dc8ba
Source dataset
uspto-grants-2010_01
Patent number
US07645771B2

Reaction notes

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