Methyl 2-chloropyridine-4-carboxylate → HCID 66731569, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 2-chloroisonicotinate (5.6 g, 32.64 mmol) and Pd(PPh3)4 (0.754 g, 0.65 mmol) in anhydrous THF (100 mL) was added (2,5-difluorobenzyl)zinc(II) bromide (0.5 M in THF) (100 mL, 50.00 mmol) dropwise under nitrogen. The reaction mixture was heated at 60° C. for 15 h. The reaction mixture was quenched by addition of methanol (50 mL) and then filtered. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate and washed with satd NH4Cl solution and brine, then dried. The solvent was evaporated under reduced pressure. The residue was suspended in ethanol, filtered and the solid washed with ethanol. The filtrate was concentrated. The residue was dissolved in MTBE (150 mL), then HCl (4 M in dioxane, (8.15 mL) and MeOH (7.5 mL) were added. The resulting suspension was stirred for 20 min, the solid collected, washed with MTBE (×2) and air dried. The solid was dissolved in DCM (200 mL) and washed with satd NaHCO3. The organic phase was dried using a phase separator and evaporated to yield methyl 2-(2,5-difluorobenzyl)isonicotinate (6.8 g, 79%). MS m/z 264 (M+H)+

Provenance & Evidence