Acetyl chloride (4.2 ml, 58.6 mmol) was added slowly and dropwise to a stirred solution of 1-aminocyclobutane-1-carboxylic acid (2.7 g, 23.4 mmol) in methanol (40 ml) at 0 °C. The reaction mixture was then warmed to room temperature and stirred continuously for about 12 hours. The reaction progress was monitored by thin layer chromatography (TLC). After completion of the reaction, the mixture was concentrated under reduced pressure to afford methyl 1-aminocyclobutane-1-carboxylate hydrochloride (3.02 g, yield: 100%) as a white solid.
To a stirred solution of 1-aminocyclobutane-1-carboxylic acid hydrochloride (3.02 g, 23.4 mmol) in tetrahydrofuran (THF, 40 ml) at 0 °C was added triethylamine (N(Et)3, 9.6 ml, 69.6 mmol) and di-tert-butyl dicarbonate ((Boc)2O, 6.4 ml, 23.8 mmol). The reaction mixture was then warmed to room temperature and stirred continuously for about 12 hours. The reaction progress was monitored by TLC. Upon completion of the reaction, saturated ammonium chloride (NH4Cl) solution was added and extracted with ethyl acetate (EtOAc, 2 x 100 mL). The combined organic phases were washed with brine, dried over anhydrous sodium sulfate (Na2SO4) and concentrated under reduced pressure to give the crude product. Purification by fast column chromatography using ethyl acetate-hexane (3:7) as eluent gave the target product (5.32 g, yield: 100%) as an oil.
1H NMR (300 MHz, DMSO-d6): δ 7.64 (s, 1H), 3.60 (s, 3H), 2.44-2.38 (m, 2H), 2.14-2.04 (m, 2H), 1.88-1.80 (m, 2H), 1.36 (s, 9H).
