Triethylamine → (3-Bromo-2-oxo-piperidin-1-yl)acetic acid benzyl ester

Participants

Reaction Steps

67.7 g (0.2 mol) of glycine benzyl ester tosylate and 61.2 ml (0.44 mol) of triethylamine are dissolved in 200 ml of methylene chloride and added in drops at 0° C. to a solution of 55.7 g (0.2 mol) of 2,5-dibromovaleric acid chloride (Okawara et al. Chem. Pharm. Bull. (1982), (30), 1225) in 200 ml of methylene chloride within 45 minutes, and it is stirred for 18 hours at room temperature. The reaction mixture is now added in drops at 0° C. to a solution of 400 ml of aqueous 32% sodium hydroxide and 2 g of tetrabutylammonium hydrogen carbonate (about 15 minutes), and it is stirred for 30 minutes. Then, the phases are separated, and the aqueous phase is extracted three times with 200 ml of dichloromethane each. The organic phases are dried on sodium sulfate, the solution is evaporated to the dry state and chromatographed on silica gel (methylene chloride). The fractions that contain the product are combined and concentrated by evaporation.

Provenance & Evidence