a) Synthesis of 1-[2-(ethoxy)-2-oxoethyl]-1-azetidinecarboxylic acid 1,1-dimethylethyl ester
To an oven-dried 250 mL round-bottomed flask under nitrogen protection was added a solution of 1-{[(1,1-dimethylethyl)oxy]carbonyl}-3-azetidinyl)acetic acid (10 g, 46.5 mmol) in ether (100 mL). N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (9.80 g, 51.1 mmol), 4-(dimethylamino)pyridine (0.568 g, 4.65 mmol), and ethanol (5.97 mL, 102 mmol) were then added sequentially. The reaction mixture was stirred at room temperature overnight. After 1 hour of reaction, the white mixture was transformed into a colorless solution and a gelatinous substance was visible at the bottom of the bottle. The reaction mixture was diluted with ether (300 mL) and washed sequentially with 1M NaHSO4 aqueous solution (150 mL) and saturated NaHCO3 aqueous solution (150 mL). The organic phase was separated, dried over MgSO4 and concentrated under reduced pressure to give tert-butyl 3-(2-ethoxy-2-oxoethyl)azetidine-1-carboxylate (10.55 g, 93% yield) as a clear, colorless liquid.MS (ES)+ m/e 244.4 [M + H]+.
