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

Participants

Reaction Steps

To a suspension of 30.9 g NaH (55%, 772 mmol) in 1000 ml DMF was added under argon atmosphere portionwise 115 g ethyl (SR)-N-benzyl-3-oxo-4-piperidine-carboxylate hydrochloride (386 mmol, commercially available) at 0-5° C. The reaction mixture was stirred for 1 h at r.t. and a solution of 45.9 ml benzylbromide (66.0 g, 386 mmol) in 200 ml DMF was added at 0° C. The reaction mixture was stirred for 1.5 h at r. t. and 200 ml sat. NaHCO3 solution were added at 0-10° C. The reaction mixture was reduced to 500 ml and 1000 ml water were added. The aqueous phase was extracted three times with 1000 ml ethyl acetate and the combined organic phases were washed with water (3×200 ml) and brine (3×200 ml). The organic phase was dried over MgSO4, filtrated and the solvent was removed under reduced pressure. The crude product was purified by chromatography over silica gel (ethyl acetate/hexane 1/8, then 1/4) to give 101 g of the product (290 mmol, 75%) as a brown oil.

Provenance & Evidence