2-Bromopyridine → 1-(Pyridin-2-yl)piperazin-2-one

HRID 2114829Notes

Reaction equation

HRID 2114829 reaction equation
C(OC(N1C=CN(C)C(=O)C1)=O)C1C=CC=CC=1.BrC1C=CC=CN=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].C(OC([N:84]1[CH2:89][CH2:88][N:87]([C:90]2[CH:95]=[CH:94][CH:93]=[CH:92][N:91]=2)[C:86](=[O:96])[CH2:85]1)=O)C1C=CC=CC=1>O1CCOCC1.ClCCl.[OH-].[OH-].[Pd+2].C(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:91]1[CH:92]=[CH:93][CH:94]=[CH:95][C:90]=1[N:87]1[CH2:88][CH2:89][NH:84][CH2:85][C:86]1=[O:96]

Participants

11

Reactant 5

HCID 79732-BromopyridineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 58009754HCID 58009754, compoundHCID 69170789HCID 69170789, compound

Product 1

HCID 218650171-(Pyridin-2-yl)piperazin-2-one

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 9942167Palladium hydroxideCatalystHCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 4-benzyloxycarbonyl-1-methyl-pyrazin-2(1H)-one (3.0 g, 12.8 mmol), 2-bromopyridine (2.02 g, 12.8 mmol), palladium acetate (0.29 g, 1.28 mmol), xantphos (1.11 g, 1.92 mmol), cesium carbonate (6.26 g, 19.2 mmol) in anhydrous dioxane (13 mL) in a sealed vessel was heated in an oil bath at 110° C. for 6 hrs. The resultant reaction mixture was cooled to room temperature, diluted with dichloromethane, filtered, and concentrated under vacuum. The residual solid was subjected to column chromatography on silica gel eluting with a ethyl acetate-hexane gradient. Concentration of appropriate fractions provide the pyridine intermediate. A mixture of 4-benzyloxycarbonyl-1-pyridin-2-ylpiperazin-2-one (1.50 g, 4.94 mmol) and Pearlmans catalyst (0.7 g) in ethanol (50 mL) was stirred under an atmosphere of hydrogen (1 atm) at room temperature for one hour. The product mixture was filtered through a pad of Celite, and concentrated under vacuum to provide the titled compound.

Workup

  1. customThe resultant reaction mixture
  2. temperaturewas cooled to room temperature
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customConcentration of appropriate fractions provide the pyridine intermediate
  6. filtrationThe product mixture was filtered through a pad of Celite
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-32d4c91a8d564ba5805550c200b3596c
Source dataset
uspto-grants-2008_10
Patent number
US07435735B2

Reaction notes

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