Cesium carbonate → 4',6'-Dimethyl-2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-one

HRID 37861Notes

Reaction equation

HRID 37861 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[NH:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]1.Cl[C:16]1[CH:21]=[C:20]([CH3:22])[CH:19]=[C:18]([CH3:23])[N:17]=1.C1(C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C(=CC=CC=2)C=CC=1P(C1C=CC=CC=1)C1C=CC=CC=1>C1(C)C=CC=CC=1.O1CCCC1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:22][C:20]1[CH:19]=[C:18]([CH3:23])[N:17]=[C:16]([N:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)[CH:21]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 30848514-Piperidone hydrochlorideHCID 125083782-Chloro-4,6-dimethylpyridine

Product 1

HCID 668513404',6'-Dimethyl-2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-oneYield 8%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Caesium carbonate (48.05 g, 141.3 mmol) was added to a solution of piperidin-4-one hydrochloride (7.6 g, 56.5 mmol) in toluene (20 mL) and stirred for 15-20 min under argon. A solution of 2-chloro-4,6-dimethyl-pyridine (4.0 g, 28.3 mmol) in tetrahydrofuran (10 mL) was added dropwise followed successively by palladium acetate (63 mg, 0.28 mmol) and (±)-(1,1′-binaphthalene-2,2′-diyl)bis(diphenylphosphine) (BINAP) (0.174 g, 0.28 mmol). The reaction mixture was heated at reflux overnight then cooled to 0° C., diluted with water and extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo to give a residue which was purified by column chromatography over silica gel (60-120 mesh) using 10% ethyl acetate in hexane as eluent to afford 4′,6′-dimethyl-2,3,5,6-tetrahydro-[1,2′]bipyridinyl-4-one (450 mg, 8%) as a yellow solid.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. extractionextracted with ethyl acetate
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customto give a residue which
  8. customwas purified by column chromatography over silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-ca5e7c2f849744208686a0462953cb86
Source dataset
uspto-grants-2013_09
Patent number
US08524705B2

Reaction notes

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