Potassium Carbonate → HCID 21460686, compound

HRID 1376099Notes

Reaction equation

HRID 1376099 reaction equation
F[C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].Cl.[NH2:12][CH2:13][C:14]([O:16][CH2:17][CH3:18])=[O:15].C(=O)([O-])[O-].[K+].[K+].CC(C)([O-])C.[K+]>O.CN1CCCC1=O>[NH2:5][C:4]1[C:3]2[C:2](=[CH:9][C:8]([F:10])=[CH:7][CH:6]=2)[NH:12][C:13]=1[C:14]([O:16][CH2:17][CH3:18])=[O:15]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 775452,4-DifluorobenzonitrileHCID 2723640Glycine ethyl ester, hydrochlorideHCID 23665647Potassium tert-butoxide2×

Product 1

HCID 21460686HCID 21460686, compoundYield 7.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
40 °C

Procedure

Under nitrogen, stir and heat a mixture of 2,4-difluorobenzonitrile (1.14 g, 8.2 mmol), ethyl glycinate hydrochloride (1.5 mg, 10.7 mmol), potassium carbonate (3.4 g, 24.6 mmol) and 1-methyl-2-pyrrolidinone (20 mL). After 2 h allow the reaction to cool to 40° C. and add potassium tert-butoxide (300 mg, 2.7 mmol). Allow the reaction to stir and for 1 h and then add additional potassium tert-butoxide (500 mg, 4.4 mmol). Cool to room temperature overnight, pour the reaction mixture onto ice. Add water to dissolve the solids in the reaction flask and add to the reaction quench. Filter off the precipitated brown solid and extract the filtrate with ethyl acetate. Wash the extract with water (2×'s), brine and dry over magnesium sulfate. Filter and concentrate under vacuum to give a residue, which is triturated with dichloromethane to afford a solid. Collect the solid, concentrate the filtrate and chromatograph the solid on silica gel (10 g, Sepack cartridge) with dichloromethane as the eluent. Collect the appropriate fractions and concentrate to obtain a solid. Combine with the previously collected solid to provide 136.7 mg (7.5%) of the title compound: MS 223(M+H).

Workup

  1. temperatureheat
  2. customthe reaction
  3. customthe reaction
  4. stirringto stir and for 1 h
  5. temperatureCool to room temperature overnight
  6. additionpour the reaction mixture onto ice
  7. additionadd to the reaction
  8. customquench
  9. filtrationFilter off the precipitated brown solid
  10. extractionextract the filtrate with ethyl acetate
  11. washWash the
  12. extractionextract with water (2×'s), brine
  13. dry with materialdry over magnesium sulfate
  14. filtrationFilter
  15. concentrationconcentrate under vacuum
  16. customto give a residue, which
  17. customis triturated with dichloromethane
  18. customto afford a solid
  19. customCollect the solid
  20. concentrationconcentrate the filtrate and chromatograph the solid on silica gel (10 g, Sepack cartridge) with dichloromethane as the eluent
  21. customCollect the appropriate fractions
  22. concentrationconcentrate
  23. customto obtain a solid

Sources & evidence

ORD record
ord-88ccde4fb7f3491b93080e38c82f8c9e
Source dataset
uspto-grants-2007_01
Patent number
US07169925B2

Reaction notes

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