反应详情

温度

60 °C

Methyl 2-chloroisonicotinate (5.6 g, 32.64 mmol) and Pd(PPh3)4 (0.754 g, 0.65 mmol) were dissolved under nitrogen in THF (100 mL) and (4-fluorobenzyl)zinc(II) chloride (0.5 M in THF) (100 mL, 50.00 mmol) was added. The brown solution was stirred at 60° C. for 19 h. The reaction was quenched by addition of methanol (50.0 mL). The solution was diluted with EtOAc and washed with NH4Cl (aq) and water. The organic layer was evaporated, dissolved in DCM and washed with NH4Cl (aq) and then dried by passage through a phase separator. The solvent was evaporated to yield a brown oil. The compound was purified in 2 runs via Biotage, SNAP 340 g KP-SIL, eluent isocratic heptane/ethyl acetate 8:2 for 2 CV, then linear gradient heptane/ethyl acetate 8:2 to 5:5 over 5 CV to yield methyl 2-(4-fluorobenzyl)isonicotinate 7.08 g (88%) as a yellow oil. 1H NMR (400 MHz, cdcl3) δ 3.92 (s, 3H), 4.18 (s, 2H), 6.94-7.02 (m, 2H), 7.19-7.27 (m, 2H), 7.65-7.69 (m, 2H), 8.68-8.71 (m, 1H). MS m/z 246 (M+H)+

1. customThe reaction was quenched by addition of methanol (50.0 mL)
2. additionThe solution was diluted with EtOAc
3. washwashed with NH4Cl (aq) and water
4. customThe organic layer was evaporated
5. dissolutiondissolved in DCM
6. washwashed with NH4Cl (aq)
7. customdried by passage through a phase separator
8. customThe solvent was evaporated
9. customto yield a brown oil
10. customThe compound was purified in 2