Hydrochloric Acid → 2,2,2-Trichloroethyl 2-[4-chloro-2-(hydroxymethyl)phenyl]azetidine-1-carboxylate

Participants

Reaction Steps

Aqueous sodium hydroxide (1 M, 2.67 mL) was added to a stirred solution of (2-azetidin-2-yl-5-chlorophenyl)methanol hydrochloride (0.312 g, 1.33 mmol) and trichloroethoxycarbonyl chloride (0.184 mL, 1.33 mmol) in dioxane (8 mL) and water (0.4 mL) at 0° C. The reaction was warmed to ambient temperature and after 1 h was acidified with 1 M HCl solution, extracted into ether, dried (Na2SO4) and evaporated in vacuo to an oil. The crude product was purified by flash column chromatography on silica (eluting with 5% methylene chloride/10-50% ethyl acetate/hexanes gradient) to give 2,2,2-trichloroethyl 2-[4-chloro-2-(hydroxymethyl)phenyl]azetidine-1-carboxylate (283 mg a colorless gum: 1H NMR (CDCl3, 400 MHz) δ 2.24 (br m, 1H), 2.78 (m, 1H), 4.20 (br s, 2H), 4.61 (br m, 2H), 4.68 (br m, 2H), 5.66 (dd, J=8.6, 6.4 Hz, 1H), 7.34 (m, 2H), 7.56 (d, J=8.1 Hz, 1H).

Provenance & Evidence