Water → 3-Benzamido-3-(4-chlorophenyl)cyclobutanecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

A solution of 3-(4-chlorophenyl)-3-hydroxycyclobutanecarboxylic acid (4 g, 0.0176 mol) and benzonitrile (8.66 mL, 0.0847 mol) in water (4.4 mL, 0.245 mol) was treated with bismuth triflate (2.32 g, 0.0035 mol) and heated to 100° C. for 16 h. After cooling to 0° C., the reaction was quenched with 1 M HCl to pH˜, dichloromethane was added, the solution was stirred vigorously and the phases were separated. The product was leached from organic layer with 1 M NaOH. This aqueous solution was acidified with to pH-3 with 6 M HCl and extracted two times with diethyl ether. The combined organic layers were dried over MgSO4, filtered and concentrated to give a light brown residue. This crude product was dissolved in diethyl ether, and diluted with n-heptane to precipitate the product. It was filtrated, washed with n-heptane and dried at 45° C. to give the product as a white crystalline solid (1.65 g, 29%). 1H NMR (DMSO-d6, 600 MHz) δ 12.25 (bs, 1H), 9.16 (s, 1H), 7.82 (d, J=7.2 Hz, 2H), 7.50-7.53 (m, 3H), 7.43-7.45 (m, 2H), 7.38 (d, J=8.7 Hz, 2H), 2.94-3.00 (m, 1H), 2.72-2.78 (m, 4H). ESI MS found for C18H16ClNO3 m/z [352.3/354, 3 (M+Na+), 330.4/332.4 (M+1), 328.2/330.2 (M−1)].

Provenance & Evidence