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

HRID 1478434Notes

Reaction equation

HRID 1478434 reaction equation
CO[C:3]([C:5]1[CH:6]=[N:7][CH:8]=[CH:9][CH:10]=1)=[O:4].[CH3:11][C:12]([CH3:14])=[O:13].C[O-].[Na+]>C1COCC1>[N:7]1[CH:8]=[CH:9][CH:10]=[C:5]([C:3](=[O:4])[CH2:11][C:12](=[O:13])[CH3:14])[CH:6]=1

Participants

5

Reactant 3

HCID 180AcetoneHCID 7151Methyl NicotinateHCID 10942334Sodium Methoxide

Product 1

HCID 3001601-(Pyridin-3-yl)butane-1,3-dioneYield 29.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methylpyridine-3-carboxylate (20.0 g, 146 mmol) in THF (200 mL) was added acetone (50 mL, 681.0 mmol). Sodium methoxide (32.7 mL of 25% w/w, 146.0 mmol) was added dropwsie at rt under N2. The mixture was stirred at rt for 72 hours, quenched with sat. NH4Cl, acidifed with 1 N HCl to pH-5. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to dryness. The crude material was purified by column chromatography (0-10% EtOAc-Hex) to provide 1-(3-pyridyl)butane-1,3-dione (7 g) as a light yellow crystalline solid. 1H NMR (400 MHz, CDCl3) δ 15.98 (s, 1H), 9.19-8.99 (m, 1H), 8.74 (dd, J=4.8, 1.7 Hz, 1H), 8.34-8.04 (m, 1H), 7.41 (ddd, J=8.0, 4.8, 0.8 Hz, 1H), 6.20 (s, 1H), 2.24 (s, 3H). ESI-MS m/z calc. 163.06, found 164.3 (M+1)+; Retention time: 0.32 minutes (3 min run).

Workup

  1. customquenched with sat. NH4Cl
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude material was purified by column chromatography (0-10% EtOAc-Hex)

Sources & evidence

ORD record
ord-479bd5db2dc04d02b38db4dbcb1de93b
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

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