Methyl 2-chloropyridine-4-carboxylate → HCID 66731807, compound

Participants

Reaction Conditions

Reaction Steps

Freshly made (2-(trifluoromethyl)benzyl)zinc(II) bromide (8.91 g, 29.28 mmol) in tetrahydrofuran (50 mL) was added to a solution of methyl 2-chloroisonicotinate (3.35 g, 19.52 mmol) and bis(tri-tert-butylphosphine)Pd(0) (0.399 g, 0.78 mmol) in tetrahydrofuran (50 mL) under nitrogen in a dried flask. The resulting red mixture was heated to 60° C. overnight (16 h). After cooling to room temperature, the reaction was quenched by the addition of 10% aq NH4Cl and diluted with ethyl acetate. After phase separation, the organic layer was washed with brine, dried over MgSO4 and evaporated. The residue was dissolved in 100 mL MTBE. Insolubles were filtered off and the filtrate was evaporated. Purification via Biotage, SNAP 340 g KP-SIL, eluent isocratic heptane/ethyl acetate 8:2 for 1 CV, then linear gradient heptane/ethyl acetate 8:2 to 5:5 over 6 CV to yield methyl 2-(2-(trifluoromethyl)benzyl)isonicotinate (4.61 g, 80%) as a yellow oil. 1H NMR (400 MHz, cdcl3) δ 3.91 (s, 3H), 4.43 (s, 2H), 7.28-7.40 (m, 2H), 7.47 (t, 1H), 7.54-7.65 (m, 1H), 7.65-7.72 (m, 2H), 8.71 (d, 1H). MS m/z 296 (M+H)+

Provenance & Evidence