3-Aminocyclobutanone hydrochloride

Step 2. 3-Aminocyclobutan-l-one hydrochloride. To a cold (0 C) mixture of 3-oxocyclobutane-l-carbonyl chloride (1.0 g, 7.54 mmol)) and benzene (10 mL) was added a solution of sodium azide (0.98 g, 15.1 mmol) in water 10 mL. The mixture was allowed to come to room temperature and stirred for 2 hours. The organic layer was separated, washed with saturated aqueous NaHCC and dried over MgS04. The organic layer was slowly heated to 60 C and stirred for an additional 1 hour. The mixture cooled to room temperature and HC1 (20%, 10 mL) was added and the mixture was heated at 90 C for 18 hours. Then, the aqueous layer was separated and the organic layer was washed with water. The combined aqueous layer was concentrated under vacuum to give 3-aminocyclobutan-l-one hydrochloride as a white solid (0.75 g, 81.8% yield). The product was carried to the next step without any further purification.General procedure for preparation of Compound 3-3: To a solution of Compound 3-2 (200 mg, 0.5 mmol) in THF (10 mL), was added DIPEA (528.9 mg, 2.6 mmol), HATU (290 mg, 0.75 mmol), and compound 3-3 (140 mg, 1.0 mmol). The mixture was stirred at room temperature overnight and poured into water (20 mL). The resulting mixture was extracted with EtOAc (30 mLx2), and concentrated to give the crude compound 3-4 (250 mg, crude).General procedure for preparation of Compound 3-2: To a solution of Compound 3-1 (300 mg, 1.76 mmol) in DCM (10 mL), was added EtOAc/HCl (2.0 mL, 4 M), and it was stirred at room temperature for 30 min. The solution was concentrated to give the Compound 3-2 (250 mg).Step 3. tert-Butyl (3-oxocyclobutyl)carbamate. Di-tert-butyl dicarbonate (1.61 g, 7.41 mmol) was added into a cold (0 C) mixture of 3-aminocyclobutan-l-one hydrochloride (750 mg, 6.17 mmol), DMF (10 mL) and Et3N (1.28 mL, 9.25 mmol). The mixture was allowed to come to room temperature and stirred for 4 hours. The mixture poured into water and extracted (3x) with EtOAc. The organics were dried over anhydrous MgS04. The solvents were removed under vacuum and the residue was purified on silica gel (Biotage; eluting solvents hexanes: EtOAc 3/1 ratio) to afford tert-butyl (3- oxocyclobutyl)carbamate as white solid (980 mg, 86.2% yield). NMR (500MHz, CDC ) delta ppm 4.89 (brs, 1H), 4.25 (brs, 1H), 3.42-3.57 (m, 2H), 3.06-3.0 (m, 2H), 1.43 (s, 9H).