Toluene → 2-Acetylamino-3,3-bis(4-fluorophenyl)propanoic acid

HRID 32871Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 32871
[C:1]([NH:4][CH:5](C(OCC)=O)[C:6]([O:8]CC)=[O:7])(=[O:3])[CH3:2].[H-].[Na+].[F:18][C:19]1[CH:24]=[CH:23][C:22]([C:25](Br)(Br)[C:26]2[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=2)=[CH:21][CH:20]=1.C1(C)C=CC=CC=1>CN1CCCC1=O.O>[C:1]([NH:4][CH:5]([CH:25]([C:26]1[CH:31]=[CH:30][C:29]([F:32])=[CH:28][CH:27]=1)[C:22]1[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=1)[C:6]([OH:8])=[O:7])(=[O:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 14041Acetamidomalonic acid diethyl esterHCID 24758Sodium hydrideHCID 23154741HCID 23154741, Verbindung

Produkt 1

HCID 119778292-Acetylamino-3,3-bis(4-fluorophenyl)propanoic acidAusbeute 76,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Versuchsvorschrift

To a solution of diethyl acetamidomalonate (1.09 g, 5 mmol) in N-methyl-2-pyrrolidone (4 mL) was added 55% sodium hydride (219 mg, 5 mmol), and the mixture was stirred at room temperature for 1 hr. Bis(4-fluorophenyl)methylene bromide (990 mg, 4 mmol) was added, and the mixture was stirred at 50° C. for 4 hrs. After completion of the reaction, toluene (20 mL) and water (10 mL) were added to the reaction mixture and the mixture was partitioned. The obtained organic layer was washed twice with water (10 mL) and concentrated. Ethanol (4.5 mL) and 2M aqueous sodium hydroxide solution (5 mL) were added to the concentrated solution, and the mixture was stirred at 90° C. for 16 hrs. The reaction mixture was allowed to cool to 25° C., toluene (8 mL) and water (5 mL) were added, and the mixture was partitioned. The aqueous layer was concentrated to a half volume, and isopropyl acetate (8 mL) and water (10 mL) were added. The mixture was adjusted to pH 1.1 with concentrated hydrochloric acid and partitioned. The organic layer was washed with water (10 mL), concentrated and dried under vacuum to give the title compound (973 mg).

Aufarbeitung

  1. stirringthe mixture was stirred at 50° C. for 4 hrs
  2. additionwere added to the reaction mixture
  3. customthe mixture was partitioned
  4. washThe obtained organic layer was washed twice with water (10 mL)
  5. concentrationconcentrated
  6. additionEthanol (4.5 mL) and 2M aqueous sodium hydroxide solution (5 mL) were added to the concentrated solution
  7. stirringthe mixture was stirred at 90° C. for 16 hrs
  8. temperatureto cool to 25° C.
  9. additiontoluene (8 mL) and water (5 mL) were added
  10. customthe mixture was partitioned
  11. concentrationThe aqueous layer was concentrated to a half volume, and isopropyl acetate (8 mL) and water (10 mL)
  12. additionwere added
  13. custompartitioned
  14. washThe organic layer was washed with water (10 mL)
  15. concentrationconcentrated
  16. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-4bb52830e22a47a1a7957e48c82aa349
Quelldatensatz
uspto-grants-2008_09
Patentnummer
US07427688B2

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