N-Cbz-hexahydro-1H-azepin-4-one

31696-09-0

83621-33-4

General procedure for the synthesis of N-CBZ-4-azepinone from ethyl 1-Cbz-5-oxoazepane-4-carboxylate: an aqueous solution of potassium hydroxide (24.6 g, 375 mmol) (400 mL) was added to an ethanolic solution of 5-benzyl 4-ethyl-5-oxo-1,4-azepanedicarboxylate (40.0 g, 125 mmol) (400 mL). The reaction mixture was heated to reflux for 2.5 hours. After completion of the reaction, it was cooled to room temperature and ethanol was removed by distillation under reduced pressure. Subsequently, the reaction mixture was diluted with 200 mL of brine and 300 mL of ethyl acetate. The organic and aqueous layers were separated and the aqueous phase was further extracted with ethyl acetate (2 x 100 mL). All organic layers were combined, washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give an orange colored oil. Purification by fast column chromatography (silica gel, 40% ethyl acetate/hexane as eluent) gave a clarified colorless oily product (22.6 g, 73% yield). The structure of the product was analyzed by 1H NMR (CDCl3, δ: 7.31-7.30, 5.12, 3.65-3.63, 2.68-2.60, 1.81-1.78) and IR (liquid, cm-1: 1698, 1475, 1454, 1442, 1423, 1331, 1320, 1295, 1270, 1241, 1191 , 1165, 1091, 900, 699) confirmed.