Tetrahydrofuran → 1-(Pyridin-3-yl)heptan-1-one

HRID 660143Notes

Reaction equation

HRID 660143 reaction equation
[CH2:1]1[CH2:5]O[CH2:3][CH2:2]1.[CH3:6][N-:7]OC.[CH2:10]([Li])[CH2:11][CH2:12][CH2:13][CH2:14]C.[NH4+].[Cl-].C([O:22][CH2:23][CH3:24])(=O)C>>[N:7]1[CH:6]=[CH:5][CH:1]=[C:2]([C:23](=[O:22])[CH2:24][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH:3]=1

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 53630747Methoxy-methyl amideHCID 178506865HCID 178506865, compound

Product 1

HCID 2227091-(Pyridin-3-yl)heptan-1-oneYield 78%

Conditions

Temperature
-78 °C

Procedure

To a solution of anhydrous THF (15 ml) containing compound 2 (1.0 g, 6.02 mmol) was added 3.08 ml (7.66 mmol) of hexyl-lithium (2.5 M in hexane) dropwise at −78° C. under N2. After the addition, the resulting solution was stirred for 30 minutes at −78° C. The mixture was allowed to warm to ambient temperature and poured into a NH4Cl solution (10 g/50 ml H2O, 0° C.). 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 3 as an oil (0.91 g, 78%). 1H-NMR (200 MHz, CDCl3): δ 9.18 (d, J=2 Hz, 1H), 8.78 (d, J=5 Hz, 2 Hz, 1H), 8.24 (dt, J=8 Hz, 2 Hz, 1H), 7.47-7.37 (m, 1H), 2.99 (t, J=7 Hz, 2H), 1.84-1.65 (m, 2H), 1.47-1.25 (m, 6H), 0.90 (bt, J=7 Hz, 3H).

Workup

  1. additionAfter the addition
  2. temperatureto warm to ambient temperature
  3. washthe organic layer was washed with a 5% NaHCO3 solution
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting residue was purified by flash chromatography (diethyl ether/PE 1:1)

Sources & evidence

ORD record
ord-12b1705982e54c33a262e20e6e3c6b1f
Source dataset
uspto-grants-2011_12
Patent number
US08084473B2

Reaction notes

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