Methanol → (2,6-Difluoro-phenyl)-[4-(6-methyl-5-nitro-pyridin-2-yl)-piperazin-1-yl]-methanone

Participants

Reaction Steps

Charge (2,6-difluoro-phenyl)-piperazin-1-yl-methanone (1.07 equiv, 1.55 moles, 350.00 g), methanol (37.06 moles, 1.50 L, 1.19 kg), triethylamine (1.79 moles, 250.00 mL, 181.50 g), 6-chloro-2-methyl-3-nitro-pyridine (1.00 equiv, 1.45 moles, 250.00 g) to a 5 L flask with over head stirrer. Stir the reaction mixture at room temperature for 0.5 hours. Slowly heat to 60° C., and continue to stir at 60° C. overnight. Add water (750 mL) drop wise while maintaining the temperature at 60° C. Allow mixture to cool to room temperature. Filter and wash cake with 2:1 methanol/water 150 mL, then twice with MTBE. Dry under reduced pressure at 45° C. to obtain (2,6-difluoro-phenyl)-[4-(6-methyl-5-nitro-pyridin-2-yl)-piperazin-1-yl]-methanone as a yellow solid (535 g).

Provenance & Evidence