[Synthesis]
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. The above obtained methyl 1-aminocyclobutane-1-carboxylate hydrochloride (3.02 g, 23.4 mmol) was dissolved in tetrahydrofuran (THF, 40 ml) at 0 °C, triethylamine (N(Et)3, 9.6 ml, 69.6 mmol) and di-tert-butyl dicarbonate ((Boc)2O, 6.4 ml, 23.8 mmol) were added. The reaction mixture was then warmed to room temperature and stirred 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. The crude product was purified by fast chromatography using ethyl acetate-hexane (3:7) as eluent to afford the target product methyl 1-((tert-butoxycarbonyl)amino)cyclobutanecarboxylate (5.32 g, yield: 100%) as an oil.1H NMR (300 MHz, DMSO-d6) data were as follows: δ 7.64 (s, 1H), 3.60 (s, 3H), and 2.44-2.38 (m, 2H), 2.14-2.04 (m, 2H), 1.88-1.80 (m, 2H), 1.36 (s, 9H). |