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

Temperature

-78 °C

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.

1. customat −78° C.
2. stirringThe reaction mixture was stirred at −78° C. for 30 min
3. temperaturethen gradually warmed to room temperature over 1 h
4. customquenched with saturated aqueous NH4Cl
5. stirringThe biphasic mixture was stirred vigorously for 5 min
6. additionthen diluted with H2O
7. extractionextracted with EtOAc (2×)
8. dry with materialThe combined organics were dried over MgSO4
9. concentrationconcentrated
10. customThe crude residue was purified by SiO2 chromatography (20% to 50% EtOAc/hexanes)

ORD record

ord-0b2d0d7b59f24109a480bd21fc331757

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329699B2