Acetic Acid → 2-Cyano-4,4-dimethyl-hepta-2,6-dienoic acid ethyl ester

HRID 28435Notes

Reaction equation

HRID 28435 reaction equation
[CH3:1][C:2]([CH3:8])([CH2:5][CH:6]=[CH2:7])[CH:3]=O.[CH2:9]([O:11][C:12](=[O:16])[CH2:13][C:14]#[N:15])[CH3:10].N1CCCCC1.C(O)(=O)C>C1(C)C=CC=CC=1>[CH2:9]([O:11][C:12](=[O:16])[C:13]([C:14]#[N:15])=[CH:1][C:2]([CH3:8])([CH3:3])[CH2:5][CH:6]=[CH2:7])[CH3:10]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 7764Ethyl cyanoacetateHCID 8082PiperidineHCID 796362,2-Dimethylpent-4-enal

Product 1

HCID 858712602-Cyano-4,4-dimethyl-hepta-2,6-dienoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 2,2-dimethyl-pent-4-enal (5.0 g, 44 mmol), cyano-acetic acid ethyl ester (5.12 mL, 48 mmol), piperidine (1.3 mL, 14 mmol) and acetic acid (4.52 mL, 80 mmol) in 170 mL of toluene was heated under reflux for 18 hours in a flask equipped with a Dean-Stark separator. Several mL of water was collected in the trap. The reaction was cooled and washed with 1N HCl, NaHCO3 and brine, successively. The organic layers were dried over Na2SO4 and concentrated to an oil. This oil was chromatographed eluting with 20% of EtOAc in hexane to give a combination of two lots total 8.3 g (91%). 1H NMR (400 MHz; CDCl3) 1.28 (s, 6H), 1.32 (t, 3H, J=7 Hz),. 2.26 (d, 2H, J=7.6 Hz), 4.27 (q, 2H, J=7.2 Hz), 5.08 (d, 1H, J=12 Hz), 5.10 (d, 1H, J=4 Hz), 5.72 (m, 1H).

Workup

  1. temperatureunder reflux for 18 hours in a flask
  2. customequipped with a Dean-Stark separator
  3. customSeveral mL of water was collected in the trap
  4. temperatureThe reaction was cooled
  5. washwashed with 1N HCl, NaHCO3 and brine
  6. dry with materialThe organic layers were dried over Na2SO4
  7. concentrationconcentrated to an oil
  8. customThis oil was chromatographed
  9. washeluting with 20% of EtOAc in hexane
  10. customto give a combination of two lots total 8.3 g (91%)

Sources & evidence

ORD record
ord-3b7e61bf261e4c4bb3f4522fff5979e2
Source dataset
uspto-grants-2008_09
Patent number
US07419981B2

Reaction notes

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