Iodine → Trifluoroacetic acid

Participants

Reaction Steps

Ethyl 1-(4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (1.1499 g, 3.66 mmol), iodine (0.929 g, 3.66 mmol), silver sulfate (1.141 g, 3.66 mmol) and MeOH (30 mL) were stirred at in a 75° C. oil bath. The reaction progress was followed by LCMS. Additional I2/Ag2SO4 (1.5 eq. each) were added. LCMS indicated some unreacted starting material while de-methylation of the methoxy group was observed. Na2S2O3 (sat., aq) was added to quench the reaction. Volatiles were removed under reduced pressure. The pot residue was taken up by EtOAc followed filtration. The separated aqueous phase was back extracted with EtOAc. The combined extracts were dried over Na2SO4, filtered and evaporated in vacuo. The resulting pot residue was purified by preparative HPLC (reverse phase, Kromasil® 100-5C18, 100×21.1 mm) eluting with acetonitrile/water+0.1% TFA (30% to 100% organic in 10 min, then to 100% for 2 min, 20 mL/min). Related fractions were pooled and evaporated under reduced pressure to afford a white solid as a TFA salt of the titled compound. LCMS calc.=439.98. found=441.05 (M+H)+. 1H NMR (CDCl3, 500 MHz) δ 8.09 (s, 1H), 7.85 (d, J=2.0 Hz, 1H), 7.37 (dd, J=8.8, 2.0 Hz, 1H), 6.88 (d, J=8.5 Hz, 1H), 4.37 (q, J=7.0 Hz, 2H), 3.95 (s, 3H), 1.38 (t, J=7.0 Hz, 3H).

Provenance & Evidence