Acetic Acid → 2-Cyano-4-ethyl-hex-2-enoic acid benzyl ester

HRID 1796830Notes

Reaction equation

HRID 1796830 reaction equation
[CH2:1]([CH:3]([CH2:6][CH3:7])[CH:4]=O)[CH3:2].[C:8]([CH2:10][C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])#[N:9].C(O)(=O)C.N1CCCCC1>>[CH2:14]([O:13][C:11](=[O:12])[C:10]([C:8]#[N:9])=[CH:4][CH:3]([CH2:6][CH3:7])[CH2:1][CH3:2])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

5

Reactant 4

HCID 176Acetic AcidHCID 73592-EthylbutyraldehydeHCID 8082PiperidineHCID 560818Benzyl 2-cyanoacetate

Product 1

HCID 695998522-Cyano-4-ethyl-hex-2-enoic acid benzyl esterYield 95%

Procedure

To a mixture of 2-ethylbutyraldehyde (2.0 mL, 16.2 mmol) and benzyl cyanoacetate (2.85 g, 16.2 mmol) at 0° C. was added acetic acid (0.1 mL, 1.62 mmol), then piperidine (0.16 mL, 1.62 mmol) dropwise. The ice bath was removed, and stirring continued for 10 minutes. Additional acetic acid (0.1 mL) and piperidine (0.16 mL) were added, followed by the additional of oven-dried 4A molecular sieves such that stirring was not impeded. The mixture was stirred 1.5 h, then partitioned between EtOAc and sat. NaHCO3 (aq). The phases were separated, and the organic phase washed with brine, dried (MgSO4), and concentrated to provide 3.96 g (95%) of 2-cyano-4-ethyl-hex-2-enoic acid benzyl ester as a colorless oil. 1H NMR (CDCl3) δ 7.39 (m, 6H), 5.28 (s, 2H), 2.60 (m, 1H), 1.62 (m, 2H), 1.40 (m, 2H), 0.88 (t, J=7.6 Hz, 6H). 13C NMR δ 168.69, 161.40, 135.01, 128.90, 128.82, 128.50, 114.11, 109.94, 68.07, 46.35, 27.30, 11.95. IR (neat) 2233, 1729 cm−1. LRMS: m/z 256.1 (M−1). Anal. Calcd for C16H19NO2: C, 74.68; H, 7.44; N, 5.44. Found: C, 74.75; H, 7.52; N, 5.50.

Workup

  1. customThe ice bath was removed
  2. additionAdditional acetic acid (0.1 mL) and piperidine (0.16 mL) were added
  3. dry with materialof oven-dried 4A molecular sieves such
  4. stirringthat stirring
  5. stirringThe mixture was stirred 1.5 h
  6. custompartitioned between EtOAc and sat. NaHCO3 (aq)
  7. customThe phases were separated
  8. washthe organic phase washed with brine
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-ffb18fca995a48b8b9f1e36df4b4080f
Source dataset
uspto-grants-2006_04
Patent number
US07030267B2

Reaction notes

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