Hydrochloric Acid → 3-Chloro-2-fluoro-5-trifluoromethyl-benzoate dicyclohexyl-ammonium

Beteiligte Stoffe

Reaktionsschritte

To a solution of 3-chloro-2-fluoro-5-trifluoromethyl-benzaldehyde (23.0 g, 101.5 mmol) in DMF (110 ml) and CH2Cl2 (110 ml) was added potassium peroxomonosulfate (62.4 g, 101.5 mmol, 1.0 equiv.) whereupon the temperature rose from 25 to 34° C. The white suspension was stirred for 2.5 h, the white solid was filtered off, the filter cake was washed with CH2Cl2 (50 ml) and the solvent was removed under vacuum. The obtained residue was dissolved in TBME (240 ml) and the pH was adjusted to 14 upon addition of NaOH (2M, 101.5 ml, 203.0 mmol, 2.0 equiv.). The aqueous phase was separated, washed with TBME (75 ml), whereas the organic phases were washed with water (75 ml). The combined aqueous phases were acidified upon addition of HCl (25%, 52.8 ml, 4.0 equiv.) and extracted with TBME (200 ml). The organic phase was washed three times with brine, whereas the aqueous phases were washed with TBME (100 ml). The combined organic phases were dried over sodium sulfate, which was filtered off, washed with TBME (50 ml) and the solvents were removed under vacuum to yield the 3-chloro-2-fluoro-5-trifluoromethyl benzoic acid as white solid (21.35 g of crude product, 86.7% yield). The crude product was dissolved in hot acetone (200 ml) and dicyclohexyl diamine (17.5 ml, 88 mmol, 1.0 equiv.) was added at reflux temperature and the mixture was stirred for 20 min, whereupon white crystals precipitated. The oil bath was removed, the suspension was slowly cooled to ambient temperature, the crystals were filtered off, washed with acetone (60 ml) and dried under vacuum until weight constancy to yield the title compound as white crystals (35.8 g, 83.2% yield). MS (EI): acid: m/z 241.0 ([M−H]−, 100%), amine: m/z 182.0 ([M+H]+, 100%). 1H-NMR (CDCl3, 400 MHz): δ 9.57 (br s, 2H), 7.96 (dd, 1H), 7.64 (dd, 1H), 3.07 (m, 2H), 2.09 (m, 4H), 1.81 (m, 4H), 1.65 (m, 2H), 1.58-1.40 (m, 4H), 1.35-1.05 (m, 6H).

Herkunft & Nachweise