Acetone → 1-(Pyridin-3-yl)butane-1,3-dione

HRID 75510

Reaction equation

HRID 75510 reaction equation
[C:1]([O:9]CC)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[H-].[Na+].[CH3:14][C:15]([CH3:17])=[O:16].Cl>C1COCC1>[N:4]1[CH:5]=[CH:6][CH:7]=[C:2]([C:1](=[O:9])[CH2:14][C:15](=[O:16])[CH3:17])[CH:3]=1

Participants

6

Reactant 4

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 69188Ethyl Nicotinate

Product 1

HCID 3001601-(Pyridin-3-yl)butane-1,3-dione

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A cooled (0° C.) solution of ethyl nicotinate (3.00 g, 2.71 ml, 19.65 mmol) in THF (10 ml) was treated with sodium hydride (60%, 1.572 g, 39.3 mmol) followed by the dropwise addition of a solution of acetone (2.282 g, 39.3 mmol, 2.89 ml) in THF (10 ml). The mixture was heated at reflux for 3 hours and then allowed to cool to RT. The mixture was acidified to ˜pH5 with 2M HCl and partitioned between EtOAc and water. The organic phase was separated and washed with water, brine, dried (MgSO4) filtered and the solvent was removed in vacuo. Purification by chromatography on silica eluting with iso-hexane/EtOAc afforded the titled compound; 1H NMR (CDCl3, 400 MHz) δ 15.97 (1H, s), 9.10 (1H, s), 8.78 (1H, d), 8.22 (1H, d), 7.49 (1H, t), 6.21 (1H, s), 2.25 (3H, s). LCMS Rt=1.13 mins; [M+H]+ 164.21 Method LowpH_v002.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3 hours
  3. custompartitioned between EtOAc and water
  4. customThe organic phase was separated
  5. washwashed with water, brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent was removed in vacuo
  9. customPurification by chromatography on silica eluting with iso-hexane/EtOAc

Sources & evidence

ORD record
ord-ebf9e313d559476a8fb1a6ce9712deae
Source dataset
uspto-grants-2014_09
Patent number
US08835444B2

Linked notes

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