Iodoethane → 5-Chloro-2-ethoxybenzoic acid

To a mixture of 5-chlorosalicylic acid (20.0 g, 116 mmol) and potassium carbonate (48.4 g, 350 mmol) in acetonitrile (300 ml) was added iodoethane (24.0 ml, 299 mmol). The mixture was heated under reflux for 24 hours. After cooling to room temperature, the mixture was filtered through a pad of celite under suction and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate (200 ml). The solution was washed with water (100 ml), washed with aqueous sodium hydroxide solution (1 M, 2×100 ml), dried over sodium sulfate, and concentrated under reduced pressure. The residue was dissolved in ethanol (200 ml) and a solution of sodium hydroxide (10.7 g, 268 mmol) in water (50 ml) was added. The mixture was heated under reflux for 90 minutes. After cooling to room temperature, the mixture was concentrated under reduced pressure. The residue was dissolved in water (100 ml) and the solution was washed with diethyl ether (2×50 ml). The solution was adjusted to pH 2 by the careful addition of concentrated hydrochloric acid. After 60 minutes, the solid was filtered and dried under reduced pressure to provide 5-chloro-2-ethoxybenzoic acid (20.4 g, 90% yield).

1. temperatureThe mixture was heated
2. temperatureunder reflux for 24 hours
3. filtrationthe mixture was filtered through a pad of celite under suction
4. concentrationthe filtrate was concentrated under reduced pressure
5. dissolutionThe residue was dissolved in ethyl acetate (200 ml)
6. washThe solution was washed with water (100 ml)
7. washwashed with aqueous sodium hydroxide solution (1 M, 2×100 ml)
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated under reduced pressure
10. dissolutionThe residue was dissolved in ethanol (200 ml)
11. temperatureThe mixture was heated
12. temperatureunder reflux for 90 minutes
13. temperatureAfter cooling to room temperature
14. concentrationthe mixture was concentrated under reduced pressure
15. dissolutionThe residue was dissolved in water (100 ml)
16. washthe solution was washed with diethyl ether (2×50 ml)
17. additionThe solution was adjusted to pH 2 by the careful addition of concentrated hydrochloric acid
18. filtrationthe solid was filtered
19. customdried under reduced pressure

ORD record

ord-eced632cd51d406d881b157c3d45aee2

Source dataset

uspto-grants-2007_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07291616B2