Hydrochloric Acid → 4-(2-Acetamido-4-fluoro-5-methylphenyl)butanoic acid

HRID 1458308Notes

Reaction equation

HRID 1458308 reaction equation
[F:1][C:2]1[C:13]([CH3:14])=[CH:12][C:5]2=[CH:6][CH2:7][CH2:8][C:9](=[O:11])[N:10]=[C:4]2[CH:3]=1.Cl.[C:16]([O:19]C(=O)C)(=[O:18])[CH3:17].[OH-].[Na+]>CO.O.C(N(CC)CC)C.C(Cl)Cl>[C:9]([NH:10][C:4]1[CH:3]=[C:2]([F:1])[C:13]([CH3:14])=[CH:12][C:5]=1[CH2:6][CH2:7][CH2:17][C:16]([OH:19])=[O:18])(=[O:11])[CH3:8]

Participants

9

Reactant 4

HCID 313Hydrochloric Acid3×HCID 7918Acetic AnhydrideHCID 14798Sodium HydroxideHCID 221019513,4-Dihydro-8-fluoro-7-methyl-2-oxo-1-benzazepine

Product 1

HCID 224449504-(2-Acetamido-4-fluoro-5-methylphenyl)butanoic acid

Reagents, catalysts & solvents 4

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent

Procedure

To 1.0 g of 3,4-dihydro-8-fluoro-7-methyl-2-oxo-1- benzazepine, 15 ml of methanol and 0.7 ml of concentrated hydrochloric acid were added and they were heated under reflux for 3 hours. After the completion of the reaction, the reaction mixture was allowed to cool and the solvent was removed under reduced pressure. To the white residue so obtained, 20 ml of methylene chloride were added, followed by the addition of 1.8 ml of triethylamine and then 0.5 ml of acetic anhydride under ice cooling. They were stirred at room temperature for 2.5 hours. After the completion of the reaction, water and a 5% aqueous hydrochloric acid solution were added to the reaction mixture, followed by extraction with chloroform. The chloroform layer was washed with a saturated aqueous solution of sodium bicarbonate and then dried over anhydrous magnesium sulfate. The solvent was then evaporated. To the residue so obtained, 8 ml of methanol and 5 ml of a 5% aqueous solution of sodium hydroxide were added and the mixture was stirred at room temperature for 30 minutes. The solvent was then distilled off under reduced pressure. To the residue so obtained, a 5% aqueous hydrochloric acid solution was added, followed by extraction with ethyl acetate. The ethyl acetate layer was washed with saturated saline and then dried over anhydrous magnesium sulfate. The solvent was then evaporated. The residue so obtained was recrystallized from ethyl acetate-chloroform, whereby 0.8 g of the title compound was obtained.

Workup

  1. temperaturethey were heated
  2. temperatureunder reflux for 3 hours
  3. customAfter the completion of the reaction
  4. temperatureto cool
  5. customthe solvent was removed under reduced pressure
  6. customTo the white residue so obtained
  7. extractionfollowed by extraction with chloroform
  8. washThe chloroform layer was washed with a saturated aqueous solution of sodium bicarbonate
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was then evaporated
  11. customTo the residue so obtained
  12. stirringthe mixture was stirred at room temperature for 30 minutes
  13. distillationThe solvent was then distilled off under reduced pressure
  14. customTo the residue so obtained
  15. extractionfollowed by extraction with ethyl acetate
  16. washThe ethyl acetate layer was washed with saturated saline
  17. dry with materialdried over anhydrous magnesium sulfate
  18. customThe solvent was then evaporated
  19. customThe residue so obtained
  20. customwas recrystallized from ethyl acetate-chloroform

Sources & evidence

ORD record
ord-8f2cb21adeb6476d9c078c93c5c93e98
Source dataset
uspto-grants-1998_12
Patent number
US05849945

Reaction notes

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