Oxalyl chloride → N-(6-acetyl-2-chloro-3-methoxyphenyl)-5-isopropylisoxazole-3-carboxamide

HRID 925964Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 925964
[CH:1]([C:4]1[O:8][N:7]=[C:6]([C:9]([OH:11])=O)[CH:5]=1)([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[NH2:18][C:19]1[C:24]([Cl:25])=[C:23]([O:26][CH3:27])[CH:22]=[CH:21][C:20]=1[C:28](=[O:30])[CH3:29].C([O-])(O)=O.[Na+]>C(Cl)Cl.O1CCOCC1.CN(C=O)C>[C:28]([C:20]1[C:19]([NH:18][C:9]([C:6]2[CH:5]=[C:4]([CH:1]([CH3:2])[CH3:3])[O:8][N:7]=2)=[O:11])=[C:24]([Cl:25])[C:23]([O:26][CH3:27])=[CH:22][CH:21]=1)(=[O:30])[CH3:29]

Komponenten

8

Edukt 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 64838125-(Propan-2-yl)-1,2-oxazole-3-carboxylic acidHCID 299199881-(2-Amino-3-chloro-4-methoxyphenyl)ethanone

Produkt 1

HCID 66650637N-(6-acetyl-2-chloro-3-methoxyphenyl)-5-isopropylisoxazole-3-carboxamideAusbeute 60 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a stirred solution of 5-isopropylisoxazole-3-carboxylic acid (3.5 g, 22.6 mmol) in DCM (35 mL) was added anhydrous DMF (few drops) and oxalyl chloride (3.82 mL, 43.2 mmol) at 0° C. under nitrogen. At the end of the gas escape, the reaction mixture was allowed to warm up to room temperature. The mixture was stirred at room temperature for 2 hrs and was evaporated. Dioxane (70 mL) was added under nitrogen, followed by a solution of 1-(2-amino-3-chloro-4-methoxy-phenyl)-ethanone 201d (4.10 g, 20.6 mmol) in dioxane (15 mL). The reaction mixture was stirred at room temperature for 16 hrs. NaHCO3 was then added. The mixture was extracted with EtOAc. Organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The crude material was triturated in Et2O to yield compound 241d as a brown solid in 60% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 1.47 (s, 3H), 1.48 (s, 3H), 1.76 (brs, 1H), 2.57 (s, 3H), 3.34-3.40 (m, 1H), 3.98 (s, 3H), 6.86 (d, J=8.53 Hz, 1H), 7.64 (d, J=8.53 Hz, 1H), 8.07 (s, 1H).

Aufarbeitung

  1. customwas evaporated
  2. additionDioxane (70 mL) was added under nitrogen
  3. stirringThe reaction mixture was stirred at room temperature for 16 hrs
  4. extractionThe mixture was extracted with EtOAc
  5. dry with materialOrganics were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude material was triturated in Et2O

Quellen und Nachweise

ORD-Eintrag
ord-89d06834949a44b3a579d0482561ff54
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09284307B2

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