Aminoisobutyric acid → 2-((4-Carbamoyl-3-fluorophenyl)amino)-2-methylpropanoic acid

HRID 38753

Reaktionsgleichung

Reaktionsgleichung von HRID 38753
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([F:11])[CH:3]=1.[NH2:12][C:13]([CH3:18])([CH3:17])[C:14]([OH:16])=[O:15].C([O-])([O-])=O.[K+].[K+].C(C1CCCCC1=O)(=O)C>CN(C=O)C.O.[Cu]I>[C:6]([C:5]1[CH:9]=[CH:10][C:2]([NH:12][C:13]([CH3:18])([CH3:17])[C:14]([OH:16])=[O:15])=[CH:3][C:4]=1[F:11])(=[O:7])[NH2:8]

Komponenten

8

Edukt 4

HCID 6119Aminoisobutyric acidHCID 11430Potassium CarbonateHCID 134002-AcetylcyclohexanoneHCID 27733314-Bromo-2-fluorobenzamide

Produkt 1

HCID 666179022-((4-Carbamoyl-3-fluorophenyl)amino)-2-methylpropanoic acid

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 962WaterLösungsmittel2×HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
97.5 °C

Versuchsvorschrift

4-Bromo-2-fluorobenzamide (0.5 g, 2.29 mmol), 2 aminoisobutyric acid (0.354 g, 3.54 mmol), CuI (87 mg, 0.458 mmol), and K2CO3 (0.790 g, 5.72 mmol) were mixed in DMF (5 mL). H2O (0.5 mL) and TEA (11 mg, 0.1 mmol) were added followed by 2-acetyl cyclohexanone (60 mg, 0.428 mmol).The reaction mixture was heated to 95-100° C. for 48 h. The reaction mixture was diluted with H2O (20 mL) and the aqueous layer was washed with ethyl acetate (20 mL). The aqueous layer was acidified with 1M citric acid to pH 4 and the product was extracted with ethyl acetate (20 mL×3). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure to obtain the product. 1H NMR (DMSO, Freebase): δ (ppm) 7.55-7.45 (t, 1H), 7.20 (bs, 1H), 7.05 (bs, 1H), 6.80 (bs, 1H), 6.35-6.30 (d, 1H), 6.18-6.10 (d, 1H), 1.42 (s, 6H).

Aufarbeitung

  1. washthe aqueous layer was washed with ethyl acetate (20 mL)
  2. extractionthe product was extracted with ethyl acetate (20 mL×3)
  3. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto obtain the product

Quellen und Nachweise

ORD-Eintrag
ord-793f1188cf4d41e1a8718bd601062328
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08524755B2

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