Ethyl Bromide → 1-Ethyl-5-(pyrazin-2-yl)pyridin-2(1H)-one

HRID 1981514Notes

Reaction equation

HRID 1981514 reaction equation
[N:1]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[C:7]1[CH:8]=[CH:9][C:10](=[O:13])[NH:11][CH:12]=1.[CH3:14][C:15](C)([O-])C.[K+].BrCC>CN(C=O)C>[CH2:14]([N:11]1[CH:12]=[C:7]([C:2]2[CH:3]=[N:4][CH:5]=[CH:6][N:1]=2)[CH:8]=[CH:9][C:10]1=[O:13])[CH3:15]

Participants

5

Reactant 3

HCID 6332Ethyl BromideHCID 233188115-(Pyrazin-2-yl)pyridin-2(1H)-oneHCID 23665647Potassium tert-butoxide

Product 1

HCID 136451011-Ethyl-5-(pyrazin-2-yl)pyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 5-(2-pyrazinyl)-2(1H)-pyridone (6.5 g) and 6.6 g of potassium t-butoxide in 250 ml of dry DMF is stirred with warming until all the solid is dissolved. The stirred solution is cooled in an ice bath and 4.6 ml of bromoethane are added when the temperature reaches 5° C. The ice bath is removed and stirring is continued for 45 minutes at which time 0.5 ml of additional bromoethane is added. Stirring is continued over the weekend. 10 g of sodium bisulfate in distilled H2O are added to the reaction mixture which is filtered. The filtrate is evaporated and the residue taken up in boiling isopropanol. The isopropanol solution is treating with decolorizing charcoal and filtered while hot. The filtrate is evaporated in vacuum to remove residual DMF, resulting in the formulation of a solid. The solid is recrystallized from acetonitrile with hot filtration. The starting material crystallizes out. The acetonitrile mother liquid is evaporated and the residue chromatographed on 100 g of silica gel. The column is eluted with ethyl acetate, toluene and finally with methanol in ethyl acetate. The early fractions are discarded and the latter fractions are combined and recrystallized from hot toluene/decane and air dried, resulting in the desired 1-ethyl-5-(2-pyrazinyl)-2-pyridone, M.P. 119.5°-120.7° C.

Workup

  1. temperaturewith warming until all the solid
  2. dissolutionis dissolved
  3. temperatureThe stirred solution is cooled in an ice bath
  4. customreaches 5° C
  5. customThe ice bath is removed
  6. stirringstirring
  7. additionis added
  8. stirringStirring
  9. addition10 g of sodium bisulfate in distilled H2O are added to the reaction mixture which
  10. filtrationis filtered
  11. customThe filtrate is evaporated
  12. additionThe isopropanol solution is treating with decolorizing charcoal
  13. filtrationfiltered while hot
  14. customThe filtrate is evaporated in vacuum
  15. customto remove residual DMF
  16. customresulting in the formulation of a solid
  17. customThe solid is recrystallized from acetonitrile with hot filtration
  18. customThe starting material crystallizes out
  19. customThe acetonitrile mother liquid is evaporated
  20. customthe residue chromatographed on 100 g of silica gel
  21. washThe column is eluted with ethyl acetate, toluene and finally with methanol in ethyl acetate
  22. customrecrystallized from hot toluene/decane and air
  23. customdried

Sources & evidence

ORD record
ord-f01fb82674d04423a97cfe20ae79dcd8
Source dataset
uspto-grants-1986_06
Patent number
US04593028

Reaction notes

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