反应详情

温度

60 °C

Methyl 2-chloroisonicotinate (5.600 g, 32.64 mmol) and Pd(PPh3)4 (0.754 g, 0.65 mmol) were dissolved in THF (100 mL) under nitrogen, then (3,5-difluorobenzyl)zinc(II) chloride (0.5 M in THF, 100 mL, 50.00 mmol) was added and the resulting solution was stirred at 60° C. for 3 h before it was cooled to room temperature and quenched with methanol (50.0 mL). The mixture was diluted with EtOAc and washed with satd NH4Cl. The organic phase was dried and concentrated. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column, eluent isocratic heptane/EtOAc 8:2 for 2 CV, then a gradient from 20% to 50% of EtOAc in heptane over 6 CV was used as mobile phase. Methyl 2-(3,5-difluorobenzyl)isonicotinate (7.42 g, 86%) was isolated as an oil. 1H NMR (400 MHz, cdcl3) δ 3.94 (s, 3H), 4.18 (s, 2H), 6.66 (tt, 1H), 6.74-6.82 (m, 2H), 7.67-7.75 (m, 2H), 8.67-8.75 (m, 1H). MS m/z 264 (M+H)+

1. temperaturewas cooled to room temperature
2. customquenched with methanol (50.0 mL)
3. additionThe mixture was diluted with EtOAc
4. washwashed with satd NH4Cl
5. customThe organic phase was dried
6. concentrationconcentrated
7. customThe residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column, eluent isocratic heptane/EtOAc 8:2 for 2 CV