Hydrochloric Acid → HCID 59192517, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred and cooled solution of 2-fluoro-3-chloro-phenol (21.9 g, 0.15 mol) and succinic anhydride (15.3 g, 0.15 mol) in 1,1,2,2-tetrachloroethane (135 mL) was added anhydrous aluminum chloride (38.7 g, 0.29 mol) portion-wise. The reaction mixture was stirred at room temperature for 3 hours and then heated at 130° C. for 2 hours. After being cooled to room temperature, to the reaction mixture were added concentrated hydrochloric acid and ice alternatively in small portions. The resulting mixture was extracted with ethyl acetate (75 mL×3). The combined organic layers were evaporated. The solid residue was basified by slow addition of an aqueous solution of 2N sodium hydroxide solution under cooling conditions, and then extracted with ethyl acetate (30 mL×3). The aqueous layer was acidified by dropwise addition of concentrated hydrochloric acid to a pH of about 2, and then extracted with ethyl acetate (50 mL×3). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo. Column chromatography (silica gel, 100-120 mesh, 15% ethyl acetate in hexane) gave 4-(4-chloro-3-fluoro-2-hydroxy-phenyl)-4-oxo-butyric acid (7.0 g, 19%). 1H NMR (400 MHz, DMSO-d6) δ ppm 2.59 (t, J=6.26 Hz, 2H), 3.31 (t, J=6.28 Hz, 2H), 7.15 (d, J=6.56 Hz, 1H), 7.74 (d, J=6.56 Hz, 1H), 11.90-12.31 (m, 2H).

Provenance & Evidence