Hydrochloric Acid → 3-Chloro-2-fluoro-5-(trifluoromethyl)benzoic acid

Temperature

50 °C

To an aqueous solution of sodium hypochlorite (15.3 ml, 25.7 mmol, 1.2 equiv.) and sodium bromide (2.6 g, 25.7 mmol, 1.2 equiv.) in sodium hydroxide solution (47%, 2.73 ml, 32.12 mmol, 1.50 equiv.) and water (12.5 ml) was added slowly (during 25 min) at 50° C. 3-chloro-2-fluoro-5-trifluoromethyl-benzaldehyde (5.0 g, 21.4 mmol). The reaction mixture was stirred at 50° C. for 60 min, cooled to ambient temperature and quenched upon addition of aqueous sodium sulfite solution (20%, 16.2 ml, 25.7 mmol, 1.2 equiv.) to give a light turbid suspension and stirred for 1 h. The suspension was stirred for 15 min, treated with HCl (37%, 4.0 ml, 47.3 mmol, 2.21 equiv.) adjusting the pH to 1, whereupon a white precipitate formed. This precipitate was extracted with TMBE (30 ml), the organic phase was washed with brine (30 ml), whereas the aqueous phase was washed with TBME (30 ml). The combined organic phases were dried over sodium sulfate, filtered and the solvent was removed under vacuum to give the crude product as light yellow solid (5.12 g, 98.6% yield). The crude product was dissolved in hot methylcyclohexane (25 ml), and the solution was cooled to ambient temperature, whereupon white crystals precipitated. The crystals were filtered off with suction on a funnel with a fritted disk, washed with methylcyclohexane (5 ml) dried under vacuum until weight constancy to give the title compound as white crystals (4.27 g, 81.6% yield).

1. temperaturecooled to ambient temperature
2. customto give a light turbid suspension
3. stirringstirred for 1 h
4. stirringThe suspension was stirred for 15 min
5. customwhereupon a white precipitate formed
6. extractionThis precipitate was extracted with TMBE (30 ml)
7. washthe organic phase was washed with brine (30 ml), whereas the aqueous phase
8. washwas washed with TBME (30 ml)
9. dry with materialThe combined organic phases were dried over sodium sulfate
10. filtrationfiltered
11. customthe solvent was removed under vacuum
12. customto give the crude product as light yellow solid (5.12 g, 98.6% yield)
13. temperaturethe solution was cooled to ambient temperature, whereupon white crystals
14. customprecipitated
15. filtrationThe crystals were filtered off with suction on a funnel with a fritted disk
16. washwashed with methylcyclohexane (5 ml)
17. customdried under vacuum until weight constancy

ORD record

ord-504830afbd4649408254f449b4276325

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329939B2