Chloroacetyl chloride → Benzyl 4-(3-oxo-4-morpholinyl)piperidin-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Benzyl 4-[(2-hydroxyethyl)amino]piperidin-1-carboxylate (7.5 g) obtained in Example 7a) and triethylamine (4.1 mL) were dissolved in THF (70 mL), chloroacetyl chloride (2.2 mL) was added dropwise thereto with cooling at 0° C., and the mixture was stirred at 0° C. for 2 hours. The solvent was distilled off under reduced pressure, the residue was diluted with water, and the mixture was extracted with ethyl acetate. The extract was washed with a 5% aqueous citric acid solution and a saturated saline solution, and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was dissolved in DMF (60 mL), the solution was cooled to 0° C., and then sodium hydride (60% in oil; 1.2 g) was added to the reaction mixture. The mixture was stirred at 0° C. for one hour, at room temperature for one hour and at 80° C. for 15 hours. The reaction mixture was concentrated under reduced pressure, water was added thereto, the solution was acidified with 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated saline solution, and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1 to ethyl acetate) to obtain the title compound (3.8g, 44%) as a colorless oil.

Provenance & Evidence