Methyl iodide → (2S,4S)-4-(dibenzylamino)-2-methylcyclohexanone (2R,4R)-4-(dibenzylamino)-2-methylcyclohexanone

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Reaction Steps

A solution of 4-(dibenzylamino)cyclohexanone (4 g, 13.63 mmol) in THF (27 mL) was added to KHMDS/toluene (32.7 mL, 16.36 mmol) at ambient temperature. The mixture was stirred for 15 min at ambient temperature. Triethylborane (1M in THF, 17.72 mL, 17.72 mmol) was added dropwise and the mixture was allowed to stir an additional 30 min. Iodomethane (1.6 mL, 25.7 mmol) was added and the mixture was stirred for 20 hr at ambient temperature. Aqueous 1M NaOH solution was added (˜25 mL) and the mixture was vigorously stirred for 3 hr. The mixture was extracted with EtOAc (4ט100 mL) and the combined organic layers were washed with brine, dried over Na2SO4, filtered off, and concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, 125 g, EtOAc/hexane=0/100 to 20/80]. Fractions were combined and concentrated in vacuo providing (2S,4S)-4-(dibenzylamino)-2-methylcyclohexanone/(2R,4R)-4-(dibenzylamino)-2-methylcyclohexanone as a highly viscous oil, which became partially a white solid. Yield: 3.1 g. LCMS (m/z): 308.2 [M+H]+; Retention time=0.65 min (major isomer). Ratio major/minor isomer: ˜9:1.

Provenance & Evidence