Benzyl Bromide → (SR)-1,4-dibenzyl-3-oxo-piperidine-4-carboxylic acid ethyl ester

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Reaction Steps

A mixture of 38.3 g (341.0 mmol) potassium tert.-butoxide and 625 ml absolute tetrahydrofuran was stirred at room temperature for 0.5 h. The resulting milky solution was cooled to 0° C. and then 50.0 g (168.0 mmol) ethyl N-benzyl-3-oxo-4-piperidine carboxylate hydrochloride were added via a powder dropping funnel. The temperature was kept below 5° C. The mixture was warmed up to room temperature and further stirred for 1 h resulting in a yellow solution. After cooling to 0° C., a solution of 30.2 g (176.0 mmol) benzyl bromide in 20.0 ml of absolute tetrahydrofuran was dropwise added in 0.5 h. A maximum temperature of 2° C. was observed. The reaction mixture was warmed to room temperature and stirred for 4 h. The reaction solution was cooled to 0° C. and 200 ml saturated ammonium chloride solution was slowly added. After extraction and phase separation, the aqueous phase was extracted twice with 100 ml of ethyl acetate. The combined organic phase were washed twice with 100 ml of saturated sodium chloride solution, dried over Na2SO4, the solvent evaporated under reduced pressure and the residue dried to yield 58.3 g (99.3%) crude product. MS (ISP): 352 (100, [M+H]+), 174 (15).

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