反应详情

温度

100 °C

A mixture of methyl 2-chloroisonicotinate (5 g, 29.14 mmol), 3,4-difluorophenylboronic acid (5.06 g, 32.05 mmol), potassium carbonate (2.416 g, 17.48 mmol) and PdCl2 (dppf) (1.066 g, 1.46 mmol) was stirred in methanol (30 mL) and heated in a single-node microwave reactor at 100° C. for 30 min. The solvent was evaporated in vacuo. DCM (400 mL) and 8% NaHCO3 (aq) (400 mL) were added, shaken and the phases separated. The aqueous phase was extracted with DCM (400 mL). The combined organic phases were dried with a phase separator and evaporated in vacuo. The residue was purified by automated flash chromatography on three Biotage® KP-SIL 100 g columns. A gradient from 5% EtOAc in heptane over 2 CV followed by 5% to 20% of EtOAc in heptane over 9 CV was used as mobile phase. Methyl 2-(3,4-difluorophenyl)isonicotinate (5.82 g, 80%) was isolated as a white solid. 1H NMR (400 MHz, cdcl3) δ 4.00 (s, 3H), 7.23-7.33 (m, 1H), 7.76-7.84 (m, 2H), 7.90-8.00 (m, 1H), 8.21-8.27 (m, 1H), 8.82 (dd, 1H).

1. customThe solvent was evaporated in vacuo
2. additionDCM (400 mL) and 8% NaHCO3 (aq) (400 mL) were added
3. customthe phases separated
4. extractionThe aqueous phase was extracted with DCM (400 mL)
5. customThe combined organic phases were dried with a phase separator
6. customevaporated in vacuo
7. customThe residue was purified by automated flash chromatography on three Biotage® KP-SIL 100 g columns