N-Fluorobenzenesulfonimide → 4-[5-(3,5-Dichloro-phenyl)-4-fluoro-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid tert-butyl ester

HRID 1505275Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1505275
[C:1]([O:5][C:6](=[O:31])[C:7]1[CH:12]=[CH:11][C:10]([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:21])([F:20])[F:19])[O:15][N:14]=2)=[CH:9][C:8]=1[CH3:30])([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:52])(=O)=O)=CC=1>O1CCCC1>[C:1]([O:5][C:6](=[O:31])[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:17]([F:52])[C:16]([C:22]3[CH:23]=[C:24]([Cl:29])[CH:25]=[C:26]([Cl:28])[CH:27]=3)([C:18]([F:20])([F:19])[F:21])[O:15][N:14]=2)=[CH:9][C:8]=1[CH3:30])([CH3:4])([CH3:3])[CH3:2]

Komponenten

5

Edukt 3

HCID 588007N-FluorobenzenesulfonimideHCID 2733832Lithium HexamethyldisilazideHCID 595634964-[5-(3,5-Dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid tert-butyl ester

Produkt 1

HCID 583386134-[5-(3,5-Dichloro-phenyl)-4-fluoro-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid tert-butyl esterAusbeute 38,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid tert-butyl ester (preparation of similar compounds described in, for example, EP 1,731,512) (500 mg) in tetrahydrofuran (6 ml) that was stirred at −78° C. for 15 minutes under argon, was slowly added lithium bis(trimethyl-silyl)amide (“LiHMDS”) (1M in hexane) (1.1 ml). The reaction mixture was stirred at −78° C. for 1.5 hours. Then N-fluorobenzenesulfonimide (“NFSI”) (433 mg) was added quickly and the reaction mixture was stirred at −78° C. for 2 hours. The reaction was quenched by addition of aqueous ammonium chloride (saturated) at −78° C. tent-Butyl methyl ether (“TBME”) was added and the phases were separated. The organic layer was washed successively with aqueous ammonium chloride (saturated) and brine, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: dichloromethane/heptane 1:2) to give 4-[5-(3,5-dichloro-phenyl)-4-fluoro-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid tert-butyl ester (200 mg) as a colorless oil.

Aufarbeitung

  1. customwas stirred at −78° C. for 15 minutes under argon
  2. stirringthe reaction mixture was stirred at −78° C. for 2 hours
  3. customThe reaction was quenched by addition of aqueous ammonium chloride (saturated) at −78° C. tent-Butyl methyl ether (“TBME”)
  4. additionwas added
  5. customthe phases were separated
  6. washThe organic layer was washed successively with aqueous ammonium chloride (saturated) and brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography on silica gel (eluent: dichloromethane/heptane 1:2)

Quellen und Nachweise

ORD-Eintrag
ord-43f4e6ce95264869adbc8927100ed74d
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09216973B2

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