反应详情

To a solution of 1-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine (20 mg, 0.067 mmol) produced in Example (8b) in tetrahydrofuran (1 mL) were added cyclobutanone (7.0 mg, 0.1 mmol), sodium triacetoxyborohydride (28 mg, 0.13 mmol) and acetic acid (4 mg, 0.067 mmol) in that order, followed by stirring for 30 minutes at room temperature. Saturated aqueous solution of sodium hydrogencarbonate was added to the reaction mixture, extraction was performed with ethyl acetate, and the organic layer was concentrated. The resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane) to give 1-cyclobutyl-4-[2-(3,3,5,5-tetramethylcyclohexyl)phenyl]piperazine. The obtained compound was dissolved in ethyl acetate, and a 4N solution of hydrogen chloride in ethyl acetate (0.025 mL, 0.100 mmol) was added. The solution was concentrated, and hexane was added to the obtained residue to produce a solid. The solid was triturated by sonication and the supernatant hexane solution was removed. The solid residue was dried under reduced pressure to give 17.6 mg of the title compound as a white solid.

1. concentrationthe organic layer was concentrated
2. customThe resultant residue was purified by NH silica gel column chromatography (ethyl acetate/heptane)