4-Phenylpiperidine → 1-butyl-4-(4-phenylpiperidin-1-yl)pyridin-2(1H)-one

HRID 516626Notes

Reaction equation

HRID 516626 reaction equation
[C:1]1([CH:7]2[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.Br[C:66]1[CH:71]=[CH:70][N:69]([CH2:72][CH2:73][CH2:74][CH3:75])[C:68](=[O:76])[CH:67]=1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:72]([N:69]1[CH:70]=[CH:71][C:66]([N:10]2[CH2:9][CH2:8][CH:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:12][CH2:11]2)=[CH:67][C:68]1=[O:76])[CH2:73][CH2:74][CH3:75]

Participants

8

Reactant 4

HCID 698734-PhenylpiperidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 594970924-bromo-1-butylpyridin-2(1H)-one

Product 1

HCID 594970911-butyl-4-(4-phenylpiperidin-1-yl)pyridin-2(1H)-one

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

4-Phenylpiperidine (0.45 g, 2.78 mmol), palladium(II) acetate (0.016 g, 0.069 mmol), sodium tert-butoxide (0.34 g, 3.5 mmol) and BINAP (0.065 g, 0.104 mmol) were added to a solution of intermediate D6 (0.32 g, 1.39 mmol) in toluene (5 ml). The reaction mixture was heated at 100° C. for 16 hours in a sealed tube, after which it was cooled to room temperature and then diluted with water (5 ml) and extracted with EtOAc (3×5 ml). The combined organic fractions were dried (Na2SO4) and the solvent evaporated in vacuo. The crude product was purified by column chromatography (silica gel; 0-4% methanol/DCM as eluent). The desired fractions were collected and evaporated in vacuo to yield intermediate D19 (0.38 g, 89%).

Workup

  1. temperatureafter which it was cooled to room temperature
  2. extractionextracted with EtOAc (3×5 ml)
  3. dry with materialThe combined organic fractions were dried (Na2SO4)
  4. customthe solvent evaporated in vacuo
  5. customThe crude product was purified by column chromatography (silica gel; 0-4% methanol/DCM as eluent)
  6. customThe desired fractions were collected
  7. customevaporated in vacuo
  8. customto yield intermediate D19 (0.38 g, 89%)

Sources & evidence

ORD record
ord-17766ad2529e4f9f8e8dcf0d94481099
Source dataset
uspto-grants-2015_08
Patent number
US09114138B2

Reaction notes

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