Water → HCID 57447006, compound

HRID 2366588Notes

Reaction equation

HRID 2366588 reaction equation
[NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:9][CH:8]=[CH:7][CH:6]=2.[C:21](OC)(OC)(OC)[CH2:22][CH2:23][CH3:24].O>C1(C)C=CC=CC=1.ClCCl.C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1>[CH2:22]([C:21]1[N:12]([CH2:13][CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:11]2[C:10]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:4]=[CH:3][C:2]=2[N:1]=1)[CH2:23][CH3:24]

Participants

7

Reactant 3

HCID 962WaterHCID 1235121,1,1-TrimethoxybutaneHCID 57447009HCID 57447009, compound

Product 1

HCID 57447006HCID 57447006, compoundYield 62.2%

Reagents, catalysts & solvents 3

HCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)CatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of ethyl 4-[(3-aminoquinolin-4-yl)amino]butanoate (72.0 g, 263 mmol) in toluene (700 mL) was heated at reflux for 10 minutes and then cooled slightly. Trimethyl orthobutyrate (42 g, 280 mmol) and pyridinium p-toluenesulfonate (1.0 g, 4.0 mmol) were added, and the reaction was heated at reflux under a Dean-Stark trap for two hours while the distillate was periodically removed. The reaction was then stirred overnight at ambient temperature. Charcoal (5 g) was added, and the resulting mixture was heated at reflux for three hours and then filtered through a layer of CELITE filter agent. The filtrate was concentrated under reduced pressure to provide an oil that crystallized upon standing. The solid was dissolved in hot methanol (125 mL), and water (50 mL) was added. After one hour, the mixture was cooled in an ice bath to form a precipitate. The precipitate was isolated by filtration and dissolved in dichloromethane. A layer of water was present and was removed. The remaining solution was dried over potassium carbonate, filtered, and concentrated under reduced pressure to provide 53.2 g of ethyl 4-(2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)butanoate.

Workup

  1. temperatureat reflux for 10 minutes
  2. temperaturecooled slightly
  3. temperaturethe reaction was heated
  4. temperatureat reflux under a Dean-Stark trap for two hours while the distillate
  5. customwas periodically removed
  6. additionCharcoal (5 g) was added
  7. temperaturethe resulting mixture was heated
  8. temperatureat reflux for three hours
  9. filtrationfiltered through a layer of CELITE filter agent
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. customto provide an oil that
  12. customcrystallized
  13. dissolutionThe solid was dissolved in hot methanol (125 mL)
  14. additionwater (50 mL) was added
  15. waitAfter one hour
  16. temperaturethe mixture was cooled in an ice bath
  17. customto form a precipitate
  18. customThe precipitate was isolated by filtration
  19. customwas removed
  20. dry with materialThe remaining solution was dried over potassium carbonate
  21. filtrationfiltered
  22. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-89072f39338e4499bca24b27645640ec
Source dataset
uspto-grants-2014_04
Patent number
US08697873B2

Reaction notes

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