4-Phenylpiperidine → 1-(Cyclopropylmethyl)-4-(4-phenyl-1-piperidinyl)-2(1H)-pyridinone

HRID 516625Notes

Reaction equation

HRID 516625 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][CH:73]2[CH2:75][CH2:74]2)[C:68](=[O:76])[CH:67]=1>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:73]1([CH2:72][N:69]2[CH:70]=[CH:71][C:66]([N:10]3[CH2:9][CH2:8][CH:7]([C:1]4[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=4)[CH2:12][CH2:11]3)=[CH:67][C:68]2=[O:76])[CH2:74][CH2:75]1

Participants

8

Reactant 4

HCID 698734-PhenylpiperidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 585545154-Bromo-1-(cyclopropylmethyl)pyridin-2(1H)-one

Product 1

HCID 594970871-(Cyclopropylmethyl)-4-(4-phenyl-1-piperidinyl)-2(1H)-pyridinone

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 D3 (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, diluted with water (5 ml) and then 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 D18 (0.33 g, 78%).

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 D18 (0.33 g, 78%)

Sources & evidence

ORD record
ord-add3054a9e7d4f67ba321c91a9dca294
Source dataset
uspto-grants-2015_08
Patent number
US09114138B2

Reaction notes

Loading…