Ammonium Chloride → Benzyl 4-hydroxy-4-methylpiperidine-1-carboxylate

Participants

Reaction Steps

Methylmagnesium chloride (9.53 mL, 3.0M tetrahydrofuran solution) was added to tetrahydrofuran (45.5 mL). Benzyl 4-oxopiperidine-1-carboxylate (5.00 g) was dissolved in tetrahydrofuran (8.8 mL), and added dropwise to a solution of ice-cooled methylmagnesium chloride in tetrahydrofuran, and the mixture was stirred at room temperature for 14 hr. The reaction mixture was ice-cooled, aqueous ammonium chloride solution (ammonium chloride 1.41 g, water 15 mL) was added dropwise, and the mixture was partitioned and extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate, and the combined organic layer was dried over magnesium sulfate, and purified by NH-silica gel column chromatography [developing solvent; hexane:ethyl acetate=80:20 (volume ratio)→60:40 (volume ratio)]. The obtained solid was washed with isopropyl ether, and dried under reduced pressure to give the title compound (4.20 g, yield 79%) as a colorless solid.

Provenance & Evidence