Methyl pyrrole-2-carboxylate → methyl 1-{2-[4-(difluoromethoxy)phenyl]-2-oxoethyl)-1H-pyrrole-2-carboxylate

Participants

Reaction Steps

Potassium tert-butoxide (430 mg, 3.82 mmol) was added to a solution of methyl 1H-pyrrole-2-carboxylate (435 mg, 3.48 mmol), and 2-bromo-1-[4-(difluoromethoxy)phenyl]ethanone (1.01 g, 3.82 mmol) in DMF (7.5 mL) at 0° C., the resulting red suspension was stirred from 0° C. to room temperature for 18 h. The reaction mixture was diluted with EtOAc (30 mL) and water (10 mL). The organic layers were then separated and washed with further water (10 mL), dried (MgSO4) filtered and concentrated in vacuo to give an orange residue. The residue was purified by flash column chromatography (Biotage SP4, 40 g cartridge, 10%-20% EtOAc gradient in n-hexanes) to give methyl 1-{2-[4-(difluoromethoxy)phenyl]-2-oxoethyl}-1H-pyrrole-2-carboxylate as a yellow gum, (417 mg, yield 38%). 1H NMR (400 MHz, CDCl3): δ 3.69 (s, 3H), 5.69 (s, 2H), 6.23 (dd, 1H, J 4.0, 2.6 Hz), 6.60 (t, 1H, J 73.0 Hz), 6.82 (dd, 1H, J 2.5, 1.9 Hz), 7.03 (dd, 1H, J 4.0, 1.8 Hz), 7.19 (d, 2H, J 8.8 Hz), 7.97-8.03 (m, 2H).

Provenance & Evidence