Methyl 2-chloropyridine-4-carboxylate → Methyl 2-benzylisonicotinate

Participants

Reaction Conditions

Reaction Steps

Methyl 2-chloroisonicotinate (4.29 g, 25 mmol) and Pd(PPh3)4 (1.156 g, 1.00 mmol) were dissolved in THF (60 mL) to give a yellow solution. Then benzylzinc(II) bromide (0.5 M in THF) (75 mL, 37.50 mmol) was added. The resulting brown mixture was warmed to 60° C. in an oil-bath for 18 h. The reaction mixture was quenched by addition of methanol, then diluted with ethyl acetate and washed with satd NH4Cl and water. The combined organic layers were dried over MgSO4 and evaporated. The residue was purified via Biotage, Thompsson 160 g Silica, eluent isocratic heptanes/ethyl acetate 9:1 over 1 CV, then linear gradient 9:1-75:25 over 6 CV. Product containing fractions were evaporated to give methyl 2-benzylisonicotinate as an orange liquid. 1H NMR (400 MHz, cdcl3) δ 3.91 (s, 3H), 4.22 (s, 2H), 7.19-7.34 (m, 5H), 7.66 (dd, 1H), 7.69 (d, 1H), 8.70 (d, 1H).

Provenance & Evidence