Sodium hydride → 4-(3-Isopropyl-1,2,4-oxadiazol-5-YL)cyclohexan-1-one

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Reaction Steps

A mixture of N-hydroxy-isobutyramidine (Intermediate 8; 500 mg, 4.9 mmol) and 4 Å molecular sieves in tetrahydrofuran (15 mL) was stirred for 30 min at room temperature. Sodium hydride (60% dispersion; 204 mg, 5.1 mmol) was added and the mixture was heated to 60° C. for 20 min, and then cooled to room temperature. A solution of 4-oxo-cyclo-hexanecarboxylic acid ethyl ester (TCI America, Portland, Oreg., USA; 1.67 g, 9.8 mmol) in tetrahydrofuran (5 mL) was added. The reaction mixture was heated at reflux for 1 h and then cooled to room temperature and filtered. The solvent was evaporated and the residue was purified by flash chromatography, eluting with 1% methanol/dichloromethane to give 4-(3-isopropyl-[1,2,4]oxadiazol-5-yl)-cyclohexanone (630 mg, 62%) as a white solid.

Provenance & Evidence