Benzyl Alcohol → Benzyl (3-oxocyclobutyl)carbamate

Participants

Reaction Steps

To a solution of 3-oxocyclobutanecarboxylic acid (3.34 g, 29.2 mmol) in dichloromethane (29 mL) at 0° C. was added oxalyl chloride (19.0 mL, 38.0 mmol) followed by DMF (0.057 mL, 0.731 mmol). The reaction mixture was stirred for 2 h at room temperature. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in dichloromethane (15 mL). At 0° C., to the resulting solution was added sodium azide (3.23 g, 49.7 mmol) in water (7 mL) followed by tetrabutylammonium bromide. The reaction mixture was vigorously stirred for 2 h. The aqueous phase was separated and extracted with dichloromethane (2×40 mL). The combined organic portions were dried over MgSO4, filtered rapidly and benzyl alcohol (30.4 ml, 292 mmol) was added and the solvent volume was reduced under reduced pressure. The reaction mixture was heated at 95° C. for 1 h. Benzyl alcohol was removed under reduced pressure and the residue oil was purified by ISCO flash chromatography (80 g column, hexane/ethyl acetate) to give benzyl 3-oxocyclobutylcarbamate as a pale yellow solid (693 mg, 11% yield). HPLC: RT=1.16 min, 90% pure (Phenomenex, Onyx C18, 4.6×100 mm, 2 min gradient from 10% MeCN, 90% water, 0.1% TFA to 90% MeCN, 10% water, 0.1% TFA); LCMS: RT=2.37 min, 75% purity, [M+H] 220.1 (Phenominex, Luna C18, 4.6×50 mm, 4 min gradient from 10% methanol, 90% water, 0.1% TFA to 90% methanol, 10% water, 0.1% TFA); 1H NMR (500 MHz, CDCl3) δ ppm 7.32-7.38 (5H, m), 5.27 (1H, d, J=3.3 Hz), 5.12 (2H, s), 4.33 (1H, d, J=5.5 Hz), 3.40 (2H, dd, J=13.2, 6.6 Hz), 3.08 (2H, d, J=14.3 Hz). 13C NMR (101 MHz, CDCl3) δ ppm 204.50, 155.87, 136.06, 128.56 (2C, s), 128.28, 128.13 (2C, s), 66.97, 54.59 (2C, s), 37.08.

Provenance & Evidence