Reacción #64578

Ecuación de reacción

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

Rendimiento 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

Rendimiento 62.0%

Disolventes

water

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónextracted 3× with ethyl acetate
2. 2
   LavadoThe combined organic fractions were washed with brine
3. 3
   Secadodried (Na2SO4)
4. 4
   Filtraciónfiltered
5. 5
   ConcentraciónThe filtrate was concentrated
6. 6
   Otrochromatographed on silica gel (elution with 6:1 hexane-EtOAc)

Procedimiento

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)+.

Fuente