Reaktion #64578

Reaktionsgleichung

2-(2-bromo-5-nitrophenyl)-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one

methyl chlorodifluoroacetate

potassium fluoride

potassium bromide

→

title compound

Ausbeute 62.0%

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

Ausbeute 62.0%

Lösungsmittel

water

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Extraktionextracted 3× with ethyl acetate
2. 2
   WaschenThe combined organic fractions were washed with brine
3. 3
   Trocknendried (Na2SO4)
4. 4
   Filtrationfiltered
5. 5
   EinengenThe filtrate was concentrated
6. 6
   Sonstigechromatographed on silica gel (elution with 6:1 hexane-EtOAc)

Vorschrift

A mixture of 400 mg (0.606 mmol) of 2-(2-bromo-5-nitrophenyl)-4-[[2'-(N-t-butylsulfamoyl)-3-fluorobiphenyl-4-yl]methyl]-5-n-butyl-2,4-dihydro-3H-1,2,4-triazol-3-one (from Step C), 128 μL (175 mg (1.21 mmol) of methyl chlorodifluoroacetate. 42 mg (0.73 mmol) of potassium fluoride, 116 mg (0.606 mmol) of cuprous iodide, 72 mg (0.606 mmol) of potassium bromide, and 1.2 mL of DMF was stirred under N2 at 120° C. in a sealed tube for 15 hours. The cooled mixture was diluted with water and extracted 3× with ethyl acetate. The combined organic fractions were washed with brine, dried (Na2SO4), and filtered. The filtrate was concentrated, and the residue was flash chromatographed on silica gel (elution with 6:1 hexane-EtOAc) to give 243 mg (62%) of the title compound as a pale yellow foam. [Subsequently eluted was 28 mg of the 2-chloro-5-nitrophenyl analog.] The desired product was homogeneous by TLC in 5:1 hexane-EtOAc; mass spectrum (FAB) m/e 656 (M+Li)+.

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