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

Temperature

100 °C

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.

1. customThe reaction was purged with nitrogen
2. temperatureto cool to room temperature
3. additionpoured into 1 N HCl (200 mL) and EtOAc (250 mL)
4. washThe flask was rinsed with water
5. stirringThe mixture was stirred for 30 min
6. filtrationfiltered through a pad of Celite®
7. washrinsed with EtOAc
8. customThe EtOAc layer was removed
9. washwashed with aqueous sodium bisulfate and brine
10. dry with materialdried (MgSO4)
11. filtrationfiltered
12. customevaporated under vacuum

ORD record

ord-7000bc46b999496d99eb4c460784342d

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382234B2