Acetic Acid → 2-Methylene-1-pyridin-3-yl-heptan-1-one

HRID 1027513Notes

Reaction equation

HRID 1027513 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7](=[O:14])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[CH:2]=1.N1CCCC[CH2:16]1.C(O)(=O)C.C=O>CO>[CH2:16]=[C:8]([CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:7]([C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1)=[O:14]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 8082PiperidineHCID 2227091-(Pyridin-3-yl)heptan-1-one

Product 1

HCID 575480432-Methylene-1-pyridin-3-yl-heptan-1-oneYield 95%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 1 g (5.2 mmol) of compound 3, dissolved in 10 ml of MeOH, was added 0.1 ml of piperidine, 0.1 ml of acetic acid and 3 ml of an aqueous formaldehyde solution (37% formaldehyde in water). The mixture was heated to reflux for 48 hour. The mixture was cooled and concentrated in vacuo. Ethyl acetate was added and the organic layer was washed with a 5% NaHCO3 solution, dried (Na2SO4), filtered and concentrated in vacuo. The resulting residue was purified by flash chromatography (diethyl ether/PE 1/1) to give compound 4 as an oil (1.05 g, 95%). 1H-NMR (200 MHz, CDCl3): δ 8.94 (d, J=2 Hz, 1H), 8.76 (d, J=5 Hz, 2 Hz, 1H), 8.05 (dt, J=8 Hz, 2 Hz, 1H), 7.46-7.35 (m, 1H), 5.94 (s, 1H), 5.64 (s, 1H), 2.48 (bt, J=7 Hz, 2H), 1.60-1.25 (m, 6H), 0.99-0.82 (m, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 48 hour
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated in vacuo
  5. additionEthyl acetate was added
  6. washthe organic layer was washed with a 5% NaHCO3 solution
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by flash chromatography (diethyl ether/PE 1/1)

Sources & evidence

ORD record
ord-cd3b0d7b338648f3a9e9377557b0a577
Source dataset
uspto-grants-2014_05
Patent number
US08735388B2

Reaction notes

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