Hydrochloric Acid → 3-(4-Chlorobenzyl)-3-hydroxycyclobutanecarboxylic acid

Participants

Reaction Steps

In a dry flask, under argon, magnesium (1.7 g, 70.11 mmol), a crystal of I2 and just enough Et2O to cover the magnesium was heated to reflux until the purple color dissipated (ca. 10 min.). Approximately 10% of a solution of 4-chlorobenzyl chloride (11.3 g, 70.11 mmol) in Et2O (20 mL) was added all at once and reflux was continued until the solution became brown. While maintaining a gentle reflux, the remainder of the 4-chlorobenzyl chloride solution was slowly added. After the addition was complete, heating was continued for 0.5 h. The solution was cooled to room temperature and added to a solution of 3-oxocyclobutanecarboxylic acid (2 g, 17.53 mmol) in THF (30 mL) pre-cooled to 0° C. Once the addition was complete, the resulting solution was allowed to warm to room temperature with continued stirring for 16 h. The reaction mixture was then poured into a solution of ether and 1 M HCl. The layers were separated and the aqueous phase was extracted with ether (3×). The combined extracts were concentrated, dissolved in 1 M NaOH and washed with ether. The aqueous phase was re-acidified with 2 M HCl and extracted with Et2O, dried over MgSO4 and concentrated to give the subject compound as a white solid (2.5 g, 59%) of white solid. 1H NMR (CDCl3, 500 MHz) δ 7.44 (d, J=8.24 Hz, 2H), 7.35 (d, J=8.24 Hz, 2H), 3.02 (s, 2H), 2.90-2.84 (m, 1H), 2.66-2.62 (m, 2H), 2.47-2.42 (m, 2H). ESI MS found for C12H13ClO3 m/z [239.1 (M−1)].

Provenance & Evidence