Potassium Carbonate → Methyl 2-{[5-((3R)-5-Oxopyrrolidin-3-yl)-2-chlorophenyl]amino}benzoate

HRID 1799202

Reaktionsgleichung

Reaktionsgleichung von HRID 1799202
[NH2:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[CH2:13][NH:12][C:11](=[O:14])[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].Br[C:16]1[CH:25]=[CH:24][CH:23]=[CH:22][C:17]=1[C:18]([O:20][CH3:21])=[O:19].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[O:14]=[C:11]1[NH:12][CH2:13][C@@H:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([NH:1][C:16]3[CH:25]=[CH:24][CH:23]=[CH:22][C:17]=3[C:18]([O:20][CH3:21])=[O:19])[CH:3]=2)[CH2:10]1

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 11894Methyl 2-bromobenzoateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 66724932(4R)-4-(3-amino-4-chlorophenyl)pyrrolidin-2-one

Produkt 1

HCID 66725153Methyl 2-{[5-((3R)-5-Oxopyrrolidin-3-yl)-2-chlorophenyl]amino}benzoate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a mixture of (4R)-4-(3-amino-4-chlorophenyl)pyrrolidin-2-one (0.18 g, 0.86 mmol), methyl 2-bromobenzoate (0.37 g, 1.72 mmol), palladium acetate (0.038 g, 0.172 mmol), and Buchwald's reagent (2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl) (0.122 g, 0.256 mmol) was added dioxane (2 mL). The mixture was degassed by alternatively applying a vacuum and flushing with nitrogen for a few cycles. After 15 minutes, potassium carbonate (0.237 g, 1.72 mmol) was added. The mixture was stirred overnight at 100° C., and then cooled to room temperature and filtered through Celite. The filtrate was washed with an aqueous HCl solution and extracted with ethyl acetate (3 times). The ethyl acetate layers were then washed with brine and concentrated to give the title compound (13a) as a brown residue which was used directly in the next step. MS (ESI) m/z 345 (M+H)+.

Aufarbeitung

  1. customThe mixture was degassed
  2. customflushing with nitrogen for a few cycles
  3. temperaturecooled to room temperature
  4. filtrationfiltered through Celite
  5. washThe filtrate was washed with an aqueous HCl solution
  6. extractionextracted with ethyl acetate (3 times)
  7. washThe ethyl acetate layers were then washed with brine
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-b990302f28e646dc9060359215fe48a8
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08344028B2

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