Potassium Carbonate → 5-(5-chloro-2-oxo-2H-pyridin-1-yl)-pyrazine-2-carboxylic acid methyl ester

HRID 1585906Notes

Reaction equation

HRID 1585906 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:8])=[N:6][CH:7]=1.[CH3:9][O:10][C:11]([C:13]1[CH:18]=[N:17][C:16](Br)=[CH:15][N:14]=1)=[O:12].C([O-])([O-])=O.[K+].[K+].[NH4+].[Cl-]>CCOC(C)=O.O.[Cu].C1(C)C(C)=CC=CC=1>[CH3:9][O:10][C:11]([C:13]1[CH:18]=[N:17][C:16]([N:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]2=[O:8])=[CH:15][N:14]=1)=[O:12]

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 27282430Methyl 5-bromopyrazine-2-carboxylateHCID 1785160645-chloropyridin-2-ol

Product 1

HCID 538392155-(5-chloro-2-oxo-2H-pyridin-1-yl)-pyrazine-2-carboxylic acid methyl ester

Reagents, catalysts & solvents 4

HCID 23978CopperCatalystHCID 962WaterSolventHCID 7237O-XyleneSolventHCID 8857Ethyl AcetateSolvent

Procedure

5-Chloro-2-pyridinol (1.43 g, 11.05 mmol), the bromide from step 1 (2.39 g, 11.05 mmol), copper (0.021 g, 0.33 mmol) and K2CO3 (1.68 g, 12.15 mmol) were heated at 120° C. for 3 hrs. Xylene (2 ml) was added and heating was continued at 1 reflux for 2 hrs. The reaction mixture was cooled, diluted with EtOAc and water and the pH was adjusted to 9 with NH4Cl. The aqueous layer was extracted with EtOAc (2×) and the combined organic extracts were washed with brine, dried (Na2SO4) and evaporated in vacuo. The residue was chromatographed (silica gel, EtOAc: hexanes 20:80 to EtOAc: CH2Cl2 10:90 gradient elution) to afford the title compound as a solid.

Workup

  1. temperatureheating
  2. temperaturereflux for 2 hrs
  3. temperatureThe reaction mixture was cooled
  4. extractionThe aqueous layer was extracted with EtOAc (2×)
  5. washthe combined organic extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo
  8. customThe residue was chromatographed
  9. wash(silica gel, EtOAc: hexanes 20:80 to EtOAc: CH2Cl2 10:90 gradient elution)

Sources & evidence

ORD record
ord-b095ad928d384da4bcd7b8d636867f92
Source dataset
uspto-grants-1999_08
Patent number
US05939439

Reaction notes

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