Hydrochloric Acid → Methyl 2-(2,6-difluorobenzyl)isonicotinate

Participants

Reaction Conditions

Reaction Steps

Methyl 2-chloroisonicotinate (5.600 g, 32.64 mmol) and Pd(PPh3)4 (0.754 g, 0.65 mmol) were dissolved in THF (100 mL) under nitrogen and (2,6-difluorobenzyl)zinc(II) bromide (0.5 M in THF, 100 mL, 50.00 mmol) was added and the resulting solution was stirred at 60° C. for 4 h before it was cooled to room temperature and quenched with methanol (50.0 mL). The mixture was diluted with EtOAc and washed with satd NH4Cl. The organic phase was dried with MgSO4, filtered and evaporated. The crude product was dissolved in MTBE (200 mL), solids were filtered off, and HCl (4 M in dioxane, 8.16 mL, 32.64 mmol) was added dropwise. The mixture was stirred for 10 minutes before the precipitate was filtered off, washed with MTBE and dissolved in MTBE/satd NaHCO3. The organic layer was dried with MgSO4, filtered and evaporated to give methyl 2-(2,6-difluorobenzyl)isonicotinate (5.03 g, 58.6%) as a white solid. 1H NMR (400 MHz, cdcl3) δ 3.92 (s, 3H), 4.29 (s, 2H), 6.87-6.97 (m, 2H), 7.18-7.29 (m, 1H), 7.61-7.73 (m, 2H), 8.63-8.70 (m, 1H). MS m/z 264 (M+H)+

Provenance & Evidence