8-Hydroxyquinoline → 5-Chloro-3-hydroxy-2-methylbenzoic acid

Participants

Reaction Conditions

Reaction Steps

To 5-chloro-3-iodo-2-methylbenzoic acid (10.0 g, 33.7 mmol), copper(I) iodide (0.70 g, 3.68 mmol), 8-hydroxyquinoline (1.0 g, 6.89 mmol), and potassium hydroxide (9.5 g, 169 mmol) was added tert-butanol (30.0 mL), dimethyl sulfoxide (30 mL) and water (3.0 mL). The reaction was purged with nitrogen, then heated to 100° C. and stirred for 24 h. The reaction was allowed to cool to room temperature and poured into 1 N HCl (200 mL) and EtOAc (250 mL). The flask was rinsed with water. The mixture was stirred for 30 min, filtered through a pad of Celite®, and rinsed with EtOAc. The EtOAc layer was removed, washed with aqueous sodium bisulfate and brine, dried (MgSO4), filtered and evaporated under vacuum to give 5-chloro-3-hydroxy-2-methylbenzoic acid (6.5 g, 27.9 mmol, 83% yield) as a light brown solid. 1H NMR (400 MHz, DMSO-d6) δ 13.07 (br. s., 1H), 10.18 (s, 1H), 7.17 (d, J=2.27 Hz, 1H), 6.98 (d, J=2.02 Hz, 1H), 2.26 (s, 3H). MS(ES) [M+H]+ 186.9.

Provenance & Evidence