Methyl chlorodifluoroacetate → 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

Participants

Reaction Steps

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)+.

Provenance & Evidence