beta-Alanine, ethyl ester, hydrochloride → HCID 23033069, compound

HRID 490232Notes

Reaction equation

HRID 490232 reaction equation
CO[C:3](=[C:10]([C:13]#[N:14])[C:11]#[N:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.[CH2:16]([O:18][C:19](=[O:23])[CH2:20][CH2:21][NH2:22])[CH3:17]>C(#N)C.C(N(CC)CC)C>[NH2:14][C:13]1[C:10]([C:11]#[N:12])=[C:3]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:22]([CH2:21][CH2:20][C:19]([O:18][CH2:16][CH3:17])=[O:23])[C:20]=1[C:19]([O:18][CH3:16])=[O:23]

Participants

5

Reactant 2

HCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 726895HCID 726895, compound

Product 1

HCID 23033069HCID 23033069, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8471TriethylamineSolvent

Procedure

After dissolving (methoxyphenylmethylene)methane-1,1-dicarbonitrile (15.10 g) and β-alanine ethyl ester hydrochloride (15.11 g) in acetonitrile (300 mL), triethylamine (23.00 mL) was added and the mixture was stirred for 10 minutes at room temperature. After confirming complete consumption of the (methoxyphenyl-methylene)methane-1,1-dicarbonitrile by thin-layer chromatography (hexane/ethyl acetate=3/1), the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the residue, and extraction was performed 3 times with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off under reduced pressure. Acetonitrile (700 mL) and anhydrous cesium carbonate (53.65 g) were added to the residue. Methyl bromoacetate (16.00 mL) was added thereto and the mixture was heated to reflux for 40 minutes. After cooling the mixture to room temperature, it was allowed to stand, the supernatant was separated by decantation, and the solvent was distilled off under reduced pressure. The residue was combined with the solid portion remaining after decantation, ethyl acetate and water were added, and extraction was performed 3 times with ethyl acetate. The organic layer was washed with water and saturated brine and then dried over anhydrous magnesium sulfate. After filtering off the magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was passed through a chromatography column packed with a small amount of silica gel (elution with dichloromethane), for removal of the highly polar impurities, to obtain the title compound as a crude product (35.31 g).

Workup

  1. additionwas added
  2. customconsumption of the (methoxyphenyl-methylene)methane-1,1-dicarbonitrile by thin-layer chromatography (hexane/ethyl acetate=3/1)
  3. distillationthe solvent was distilled off under reduced pressure
  4. additionEthyl acetate and water were added to the residue, and extraction
  5. washThe organic layer was washed with water and saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationAfter filtering off the magnesium sulfate
  8. distillationthe solvent was distilled off under reduced pressure
  9. additionAcetonitrile (700 mL) and anhydrous cesium carbonate (53.65 g) were added to the residue
  10. additionMethyl bromoacetate (16.00 mL) was added
  11. temperaturethe mixture was heated
  12. temperatureto reflux for 40 minutes
  13. temperatureAfter cooling the mixture to room temperature
  14. customthe supernatant was separated by decantation
  15. distillationthe solvent was distilled off under reduced pressure
  16. additionwere added
  17. extractionextraction
  18. washThe organic layer was washed with water and saturated brine
  19. dry with materialdried over anhydrous magnesium sulfate
  20. filtrationAfter filtering off the magnesium sulfate
  21. distillationthe solvent was distilled off under reduced pressure
  22. custompacked with a small amount of silica gel (elution with dichloromethane), for removal of the highly polar impurities

Sources & evidence

ORD record
ord-e61e736d665e47478887165a9f59f329
Source dataset
uspto-grants-2009_05
Patent number
US07528140B2

Reaction notes

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