Methyl 2-chloropyridine-4-carboxylate → Methyl 2-(3-fluorobenzyl)isonicotinate

Participants

Reaction Conditions

Reaction Steps

Methyl 2-chloroisonicotinate (5.6 g, 32.64 mmol) and Pd(PPh3)4 (0.754 g, 0.65 mmol) were dissolved in THF (100 mL) under nitrogen and (3-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 4 h. The reaction was quenched by addition of methanol (50 mL), diluted with EtOAc and washed with NH4Cl. The organic layer was dried over Na2SO4, filtered and evaporated to yield a yellow 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-(3-fluorobenzyl)isonicotinate (6.766 g, 85%) as a yellow oil. 1H NMR (400 MHz, cdcl3) δ 3.93 (s, 3H), 4.21 (s, 2H), 6.88-7.00 (m, 2H), 7.02-7.07 (m, 1H), 7.22-7.30 (m, 1H), 7.66-7.73 (m, 2H), 8.68-8.73 (m, 1H). MS m/z 246 (M+H)+

Provenance & Evidence