Oxalyl chloride → 2-(2-fluoro-4-methanesulfonyl-phenylsulfanyl)-N-[3-(2-methoxy-1,1-dimethyl-ethyl)-isoxazol-5-yl]-2-methyl-propionamide

Participants

Reaction Conditions

Reaction Steps

Activation of 336 mg (1.15 mmol) of 2-(2-fluoro-4-methanesulfonyl-phenylsulfanyl)-2-methyl-propionic acid as its acid chloride is achieved by treatment with oxalyl chloride (0.3 mL, 3.45 mmol) and DMF (1 drop) in DCM (15 mL) at room temperature for 3 h. The solvent is removed under reduced pressure and the crude acid chloride is dissolved in toluene (5 mL) and added to a solution of 196 mg (1.15 mmol) of 3-(2-methoxy-1,1-dimethyl-ethyl)-isoxazol-5-ylamine and N,N-diisopropylethylamine (0.40 mL, 2.3 mmol) in toluene. The reaction is heated to 50° C. for 18 h. After cooling to room temperature, the reaction mixture is diluted with ethyl acetate (20 mL) and washed with 1M aqueous HCl solution (2×10 mL), water (2×10 mL), saturated aqueous NaHCO3 solution (2×10 mL), brine (10 mL). The organic layer is dried (Na2SO4), filtered and the filtrate is concentrated under reduced pressure. The residue is purified twice by column chromatography (silica, eluent: heptanes, 20-50% ethyl acetate, followed by heptanes, 10% ethyl acetate) to afford 220 mg of 2-(2-fluoro-4-methanesulfonyl-phenylsulfanyl)-N-[3-(2-methoxy-1,1-dimethyl-ethyl)-isoxazol-5-yl]-2-methyl-propionamide. Yield: 43%, ES-MS: m/z 445 [M+H]

Provenance & Evidence