Potassium Carbonate → 1-(6-Methoxypyridin-3-yl)piperidin-4-one

HRID 564359Notes

Reaction equation

HRID 564359 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[I-].C([N+]1(C)[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]1)C1C=CC=CC=1>C(O)C.O>[CH3:9][O:8][C:5]1[N:6]=[CH:7][C:2]([N:1]2[CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]2)=[CH:3][CH:4]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 811216-Methoxy-3-pyridinylamineHCID 110780641-Benzyl-1-methyl-4-oxopiperidinium iodide

Product 1

HCID 220002791-(6-Methoxypyridin-3-yl)piperidin-4-oneYield 74%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

To a solution of 5-amino-2-methoxypyridine (375 mg, 3.02 mmol) and K2CO3 (49 mg, 0.355 mmol) in ethanol (7 mL) at 80° C. was added a slurry of 1-benzyl-1-methyl-4-oxopiperidinium iodide in water (5 mL) over a 10 minute period. After 45 minutes, the reaction mixture was cooled and partitioned between dichloromethane (10 mL) and water. The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (1:1 Hexanes:EtOAc) to afford 1-(6-methoxypyridin-3-yl)piperidin-4-one (459 mg, 74%) as a light orange solid. 1H NMR (CDCl3) δ: 2.56 (t, J=5.7 Hz, 4H), 3.42 (t, J=5.7 Hz, 4H), 3.87 (s, 3H), 6.69 (d, J=9.3 Hz, 1H), 7.32 (dd, J=9.0, 3.0 Hz, 1H), 7.85 (d, J=3.0 Hz, 1H).

Workup

  1. temperaturethe reaction mixture was cooled
  2. custompartitioned between dichloromethane (10 mL) and water
  3. customThe organic layer was separated
  4. washthe aqueous layer was washed with an addition portion of dichloromethane (10 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-1cf551563beb4a59931be27a198dde47
Source dataset
uspto-grants-2011_11
Patent number
US08067457B2

Reaction notes

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