Methyl chlorodifluoroacetate → 5-n-Butyl-4-[[2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl]-2,4-dihydro-2-[5-nitro-2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-one

HRID 1198689

Reaktionsgleichung

Reaktionsgleichung von HRID 1198689
Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[N:11]1[C:15](=[O:16])[N:14]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[S:30](=[O:37])(=[O:36])[NH:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[CH:20][CH:19]=2)[C:13]([CH2:38][CH2:39][CH2:40][CH3:41])=[N:12]1.[F-:42].[K+].Cl[C:45]([F:51])([F:50])C(OC)=O>CN(C=O)C.O>[CH2:38]([C:13]1[N:14]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[S:30](=[O:36])(=[O:37])[NH:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[CH:20][CH:19]=2)[C:15](=[O:16])[N:11]([C:3]2[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=2[C:45]([F:51])([F:42])[F:50])[N:12]=1)[CH2:39][CH2:40][CH3:41]

Komponenten

6

Edukt 3

HCID 73935Methyl chlorodifluoroacetateHCID 522689Potassium FluorideHCID 100779172-(2-Bromo-5-nitrophenyl)-4-[[2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one

Produkt 1

HCID 103942615-n-Butyl-4-[[2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl]-2,4-dihydro-2-[5-nitro-2-(trifluoromethyl)phenyl]-3H-1,2,4-triazol-3-oneAusbeute 37 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of 600 mg (0.935 mmol) of 2-(2-bromo-5-nitrophenyl)-4-[[2'-(N-t-butylsulfamoyl)biphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one (from Step B) in 1.87 mL of DMF were added 65 mg (1.12 mmol) of potassium fluoride, 179 mg (0.935 mmol) of cuprous iodide, and 197 μL (270 mg, 1.87 mmol) of methyl chlorodifluoroacetate. The mixture was stirred in a sealed tube at 120° C. for 12 hours. The cooled mixture was diluted with H2O and extracted 3× with ethyl acetate. The combined organic extracts were washed with H2O, then brine, and dried over Na2SO4. The residue obtained upon evaporation of the filtered solution was flash chromatographed on silica gel (gradient elution with 8.5:1 to 5:1 hexane-EtOAc) to give 216 mg (37%) of the title compound as a solid, mp 135°-137° C. [Subsequently eluted was 187 mg (32%) of the corresponding 2-chloro-5-nitrophenyl analog, obtained as a byproduct.] The desired product was homogeneous by TLC (98:2 CH2Cl2 --MeOH); mass spectrum (FAB) m/e 638 (M+Li)+.

Aufarbeitung

  1. extractionextracted 3× with ethyl acetate
  2. washThe combined organic extracts were washed with H2O
  3. dry with materialbrine, and dried over Na2SO4
  4. customThe residue obtained upon evaporation of the filtered solution
  5. customchromatographed on silica gel (gradient elution with 8.5:1 to 5:1 hexane-EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-11a49b21a4b340b1b30b7e459ee30f3d
Quelldatensatz
uspto-grants-1994_01
Patentnummer
US05281614

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