L-Pyroglutamic Acid → (S)-5-oxo-pyrrolidine-2-carboxylic acid (3-tert-butyl-isoxazol-5-yl)-amide

Participants

Reaction Steps

To solution of the (S)-5-oxo-pyrrolidine-2-carboxylic acid (6 g, 46.47 mmol) in tetrahydrofuran (50 mL) is added thionyl chloride (6.75 ml, 92.94 mmol) and stirred at room temperature for 2-3 hours. The solvent is removed under reduced pressure and the residue is dissolved in tetrahydrofuran (20 mL) and added dropwise to a solution of 3-tert-butyl-isoxazol-5-ylamine (6.514 g, 46.47 mmol) and diisopropylamine (24.28 ml, 139.41 mmol) in tetrahydrofuran (50 mL) at room temperature. The reaction is stirred overnight at room temperature then diluted with dichloromethane and washed sequentially with water and saturated brine solution. The organics are dried over sodium sulfate, filtered and solvents removed under vacuum. The crude residue is purified by flash column chromatography eluting with 5-10% methanol/dichloromethane. The product rich fractions are pooled and evaporated to afford 3.02 g title compound, 32.7% yield. ESI m/z 252=MH+.

Provenance & Evidence