Pyrazole → 1-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1H-pyrazole-4-carboxylic acid methyl ester

HRID 1505286Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1505286
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][NH:8][CH:9]=1)=[O:4].[H-].[Na+].Cl[C:13]1[CH2:17][C:16]([C:22]2[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=2)([C:18]([F:21])([F:20])[F:19])[O:15][N:14]=1.N1C=CC=N1>C(#N)C>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[N:7][N:8]([C:13]2[CH2:17][C:16]([C:22]3[CH:27]=[C:26]([Cl:28])[CH:25]=[C:24]([Cl:29])[CH:23]=3)([C:18]([F:19])([F:20])[F:21])[O:15][N:14]=2)[CH:9]=1)=[O:4]

Komponenten

6

Edukt 4

HCID 1048PyrazoleHCID 24758Sodium hydrideHCID 9793760Methyl 1H-pyrazole-4-carboxylateHCID 584979653-Chloro-5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazole

Produkt 1

HCID 584979541-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-1H-pyrazole-4-carboxylic acid methyl esterAusbeute 100,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6342AcetonitrileLösungsmittel2×

Versuchsvorschrift

To a solution of pyrazole-4-carboxylic acid methyl ester (756 mg) in acetonitrile (30 ml) under argon was added sodium hydride (240 mg). The reaction mixture was stirred at room temperature for 1 h. 15 mf of this solution was added dropwise to a solution of chloroisoxazoline of example 17.2 (630 mg) in acetonitrile (10 ml). It was then stirred at room temperature for 1 h; 15 ml of pyrazole solution was added again and the mixture was stirred over the weekend. The reaction was quenched by adding water and dichloromethane. The two layers were separated. The aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated. The crude residue was purified by column chromatography (from c-Hex (100%) to c-Hex:EtOAc (80:20)) to afford the title intermediate (810 mg) as a yellow solid. 1H-NMR (CDCl3, 400 MHz): 8.60 (s, 1H), 8.10 (s, 1H), 7.5 (m, 2H), 7.45 (m, 1H), 4.35 (d, 1H), 4.00 (d, 1H), 3.75 (s, 3H).

Aufarbeitung

  1. stirringIt was then stirred at room temperature for 1 h
  2. stirringthe mixture was stirred over the weekend
  3. customThe reaction was quenched
  4. additionby adding water and dichloromethane
  5. customThe two layers were separated
  6. extractionThe aqueous layer was extracted with dichloromethane
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe crude residue was purified by column chromatography (from c-Hex (100%) to c-Hex:EtOAc (80:20))

Quellen und Nachweise

ORD-Eintrag
ord-3050d64d93234c30b462df3515abc61f
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09216973B2

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