Isoamyl Nitrite → (3Z)-1-benzyl-3-hydroxyimino-4,4-dimethylpiperidine-2,6-dione

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-benzyl-4,4-dimethylpiperidine-2,6-dione (1.00 g, 4.32 mmol) in THF (20 mL) at −78° C. was slowly added LiHMDS (1.0M in THF, 4.8 mL, 4.8 mmol). The resulting thick white slurry was stirred at −78° C. for 20 min then isopentyl nitrite (0.70 mL, 5.20 mmol) was added dropwise which caused a bright orange color to appear. The reaction mixture was stirred at −78° C. for 30 min then gradually warmed to room temperature over 1 h and quenched with saturated aqueous NH4Cl. The biphasic mixture was stirred vigorously for 5 min then diluted with H2O and extracted with EtOAc (2×). The combined organics were dried over MgSO4 and concentrated. The crude residue was purified by SiO2 chromatography (20% to 50% EtOAc/hexanes) to isolate first 340 mg (30%) of (Z)-1-benzyl-4,4-dimethylpiperidine-2,3,6-trione 3-oxime as a white solid followed by 280 mg (25%) of (E)-1-benzyl-4,4-dimethylpiperidine-2,3,6-trione 3-oxime as a white solid.

Provenance & Evidence