Imidazole → HCID 57888790, compound

Participants

Reaction Steps

A solution of 1-benzyl-4-(4-chlorophenyl)-3,3-dimethylpiperidin-4-ol (6.9 g, 20.92 mmol) and imidazole (0.214 g, 3.14 mmol) in THF (175 mL) was treated with sodium hydride (2.510 g, 62.8 mmol) in two portions. The mixture was heated at reflux overnight. Vigorous gas evolution was observed 20 minutes after heat was applied, before the reaction reached reflux temperature. The mixture was cooled to room temperature, and treated with carbon disulfide (23.96 mL, 397 mmol), causing the color to change to a burnt amber. The reaction was returned to reflux temperature for 2 hours. The mixture was cooled to room temperature, treated with iodomethane (1.570 mL, 25.1 mmol), and stirred at room temperature for 1.5 hours. The reaction was quenched with brine, and the mixture was extracted 3× with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate, and concentrated in-vacuo. The residue was purified over a 8×10 cm silica gel column, eluting with ethyl acetate/hexanes (5%-10%-15%-20% ethyl acetate), to yield the title compound (7.3 g, 17.38 mmol, 83% yield) as an amber oil. MS (ESI+)=421, (M+H)+.

Provenance & Evidence