Ethyl Acetate → 6-Ethyl-2,3-dihydroquinolin-4(1H)-one

HRID 1985086Notes

Reaction equation

HRID 1985086 reaction equation
O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[CH2:15]([C:17]1[CH:22]=[CH:21][C:20]([NH:23][CH2:24][CH2:25][C:26]([O:28]CC)=O)=[CH:19][CH:18]=1)[CH3:16].[OH-].[Na+].C(OCC)(=O)C>CS(O)(=O)=O.CO>[CH2:15]([C:17]1[CH:18]=[C:19]2[C:20](=[CH:21][CH:22]=1)[NH:23][CH2:24][CH2:25][C:26]2=[O:28])[CH3:16]

Participants

7

Reactant 4

HCID 8857Ethyl Acetate2×HCID 14798Sodium Hydroxide2×HCID 14812Phosphorus oxide (P4O10)2×HCID 43365416HCID 43365416, compound

Product 1

HCID 223244436-Ethyl-2,3-dihydroquinolin-4(1H)-oneYield 24.8%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6395Methanesulfonic AcidSolvent

Conditions

Temperature
130 °C

Procedure

A solution of phosphorus pentoxide (19.53 g) in methane sulfonic acid (200 mL) was heated to 130° C. The mixture was stirred at 130° C. for one hour until all the phosphorus pentoxide had dissolved. The mixuture was allowed to cool for 15 minutes and ethyl N-(4-ethylphenyl)-beta-alaninate (19.53 g of mono and di-ester mixture) was added. The mixture was heated to 130° C. for one hour and allowed to slowly cool overnight. The mixture was then cooled in an ice bath and 10N sodium hydroxide was added until the pH reached 9.5. Ethyl acetate was added to the mixture to help dissolve solids. The remaining gummy dark solids were dissolved in methanol and added to the ethyl acetate-aq. sodium hydroxide mixture. Semi-crystalline solids precipitated and were removed by filtration through Celite. The filtrate was washed with water, followed by 1N sodium hydroxide and brine, dried with magnesium sulfate, filtered, and concentrated. Silica gel chromatography using 0.25% ammonium hydroxide in dichloromethane gave mixed fractions. The mixed fractions were combined and re-chromatographed using 30% ethyl acetate in heptane. The resulting material was further upgraded by formation of the hydrochloride salt using 2N HCl in ether. The salt was collected by filtration and washed with heptane and dried in an oven under vacuum at 50° C. overnight. The salt was then partitioned between dichloromethane and 1N sodium hydroxide. The organic layer was extracted twice with dichloromethane, washed with 1N sodium hydroxide, dried with sodium sulfate, filtered, and concentrated to give 3.83 g of the title compound. MS (ESI+) for C11H13NO m/z 175.96 (M+H)+.

Workup

  1. dissolutionhad dissolved
  2. temperatureto cool for 15 minutes
  3. temperatureThe mixture was then cooled in an ice bath
  4. dissolutionto help dissolve solids
  5. customSemi-crystalline solids precipitated
  6. customwere removed by filtration through Celite
  7. washThe filtrate was washed with water
  8. dry with materialdried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customgave
  12. additionmixed fractions
  13. customre-chromatographed
  14. filtrationThe salt was collected by filtration
  15. washwashed with heptane
  16. customdried in an oven under vacuum at 50° C. overnight
  17. customThe salt was then partitioned between dichloromethane and 1N sodium hydroxide
  18. extractionThe organic layer was extracted twice with dichloromethane
  19. washwashed with 1N sodium hydroxide
  20. dry with materialdried with sodium sulfate
  21. filtrationfiltered
  22. concentrationconcentrated

Sources & evidence

ORD record
ord-b78fb1ba1ed14cc19c28b9a587f623a6
Source dataset
uspto-grants-2009_06
Patent number
US07544717B2

Reaction notes

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