Hydrochloric Acid → 1-Tert-butyl 4-ethyl 4-(3-(benzyloxy)propyl)piperidine-1,4-dicarboxylate

Participants

Reaction Steps

To a solution of 1.2 mL of diisopropylamine in 20 mL of tetrahydrofuran, 5.8 mL of a 1.6 mol/L butyryl lithium/hexane solution was dropped at −78° C., and the mixture was stirred at the same temperature for 1 hour. Thereto was dropped a solution of 2.0 g of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate in 2 mL of tetrahydrofuran, and the mixture was stirred for 1 hour. Thereto was added 1.7 mL of benzyl 3-bromopropyl ether, and the temperature of the reaction mixture was increased to room temperature and the mixture was stirred for 10 hours. The mixture was charged with water and adjusted to pH 2.0 with 6 mol/L hydrochloric acid. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The organic layer and the extract were combined, the resultant solution was washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography using an eluent of hexane:ethyl acetate=10:1 to obtain 2.0 g of 1-tert-butyl 4-ethyl 4-(3-(benzyloxy)propyl)piperidine-1,4-dicarboxylate as a colorless oily substance.

Provenance & Evidence