Iodine → Ethyl 1-[6-(2-hydroxy-3-iodophenyl)pyridin-2-yl]-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

Participants

Reaction Steps

To a suspension of the title compound from Example 1 Step B (2.00 g, 5.30 mmol) and silver sulfate (1.653 g, 5.30 mmol) in EtOH (53 mL) was added iodine (1.35 g, 5.30 mmol). The resulting suspension was stirred vigorously at ambient temperature. After 4 h, the reaction mixture was diluted with EtOAc, and the organic phase was washed successively with water, sat. aq. sodium bisulfate, and sat. aq. NaHCO3. The organic phase was then concentrated in vacuo. The title compound was separated from the para-iodo isomer upon purification by flash chromatography on silica gel (0 to 15% EtOAc in hexanes, then 15% EtOAc in hexanes, then 15 to 100% EtOAc in hexanes; the title compound is the later eluting isomer): LCMS m/z 504.5 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 13.08 (s, 1H), 8.17 (s, 1H), 8.10 (t, J=8.0 Hz, 1H), 8.06 (d, J=8.0 Hz, 1H), 7.86 (dd, J=7.5, 1.5 Hz, 1H), 7.82 (dd, J=8.0, 1.5 Hz, 1H), 7.52 (d, J=7.5 Hz, 1H), 6.75 (t, J=8.0 Hz, 1H), 4.33 (q, J=7.0 Hz, 2H), 1.43 (t, J=7.0 Hz, 3H).

Provenance & Evidence