Water → Methyl 5-chloro-2-(4-fluorobenzyl)nicotinate

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of methyl 2,5-dichloronicotinate (Journal of Chemical and Engineering Data 1981, 26, 332, 350 mg, 1.70 mmol) and tetrakis(triphenylphosphine)palladium(0) (196 mg, 0.17 mmol) in tetrahydrofuran (6 mL) was added a 0.5 M solution of 4-fluorobenzylzinc chloride in tetrahydrofuran (4.08 mL, 2.04 mmol) at 0° C. under nitrogen. The resulting mixture was heated at 60° C. for 16 h. The mixture was poured into water (50 mL) and the aqueous mixture was extracted with ethyl acetate (100 mL). The organic layer was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by flush column chromatography on silica gel eluting with hexane/ethyl acetate (6/1) to afford 416 mg (88%) of the title compounds as colorless oil: 1H-NMR (CDCl3) δ 8.64 (1H, d, J=2.6 Hz), 8.17 (1H, d, J=2.6 Hz), 7.24–7.20 (2H, m), 6.96–6.90 (2H, m), 4.50 (2H, s), 3.89 (3H, s).

Provenance & Evidence