反应详情

To a solution of 3-chloro-2-fluoro-5-trifluoromethyl-benzaldehyde (4.2 g, 18.5 mmol) in DMF (21 ml) and CH2Cl2 (21 ml) was added potassium peroxomonosulfate (11.4 g, 18.5 mmol, 1.0 equiv.) whereupon the temperature rose from 25 to 34° C. The white suspension was stirred for 2 h, the white solid was filtered off, the filter cake was washed with CH2Cl2 (25 ml) and the solvent was removed under vacuum. The obtained residue was dissolved in TBME (50 ml) and the pH was adjusted to 14 upon addition of NaOH (2M, 22.7 ml, 45.4 mmol, 2.45 equiv.). The aqueous phase was separated, washed with TBME (25 ml), whereas the organic phases were washed with water (25 ml). The combined aqueous phases were acidified upon addition of HCl (37%, 8.4 ml, 5.35 equiv.) and extracted with TBME (50 ml). The organic phase was washed three times with brine (75 ml), whereas the aqueous phases were washed with TBME (25 ml). The combined organic phases were dried over sodium sulfate, which was filtered off, washed with TBME (20 ml) and the solvents were removed under vacuum to yield the 3-chloro-2-fluoro-5-trifluoromethyl benzoic acid as white solid (4.2 g of crude product, 93.4% yield). The crude product was dissolved in hot methyl cyclohexane (20 ml), the oil bath was removed and the suspension was slowly cooled to ambient temperature, whereupon white crystals precipitated. The white suspension was stirred in an ice bath for 2 h, the crystals were filtered off, washed with methyl cyclohexane (5 ml) and dried under vacuum until weight constancy to yield the title compound as white crystals (3.1 g, 68.9% yield).

1. customrose from 25 to 34° C
2. filtrationthe white solid was filtered off
3. washthe filter cake was washed with CH2Cl2 (25 ml)
4. customthe solvent was removed under vacuum
5. dissolutionThe obtained residue was dissolved in TBME (50 ml)
6. customThe aqueous phase was separated
7. washwashed with TBME (25 ml), whereas the organic phases
8. washwere washed with water (25 ml)
9. extractionextracted with TBME (50 ml)
10. washThe organic phase was washed three times with brine (75 ml)
11. washwhereas the aqueous phases were washed with TBME (25 ml)
12. dry with materialThe combined organic phases were dried over sodium sulfate, which
13. filtrationwas filtered off
14. washwashed with TBME (20 ml)
15. customthe solvents were removed under vacuum