Oxalyl chloride → N-(3-tert-butyl-isoxazol-5-ylmethyl)-2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionamide

Participants

Reaction Steps

Activation of 51 mg (0.22 mmol) of 2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionic acid as the corresponding acid chloride is achieved by treatment with oxalyl chloride (0.04 mL) and DMF (1 drop) in DCM (2 mL) at room temperature for 1 h. The reaction is concentrated under reduced pressure. The crude acid chloride is dissolved in DCM (1 mL) and added dropwise to a solution of (3-tert-butyl-1,2-oxazol-5-yl)methanamine (42 mg, 80%, 0.22 mmol) and N,N-diisopropylethylamine (114 μL, 0.66 mmol) in DCM (2 mL). The reaction is concentrated under reduced pressure. The residue is purified twice by column chromatography (silica, eluent: heptanes, 0-50% ethyl acetate then DCM, 20% ethyl acetate), followed by preparative HPLC (neutral method) to give 36 mg of N-(3-tert-butyl-isoxazol-5-ylmethyl)-2-methyl-2-(tetrahydro-pyran-4-sulfonyl)-propionamide. Yield: 44%; ES-MS: m/z 373 [M+H]. Compounds in Table 4 amide method D are made according to this procedure.

Provenance & Evidence