Pyridine → Benzyl (2,4-difluorophenyl)carbamate

Participants

Reaction Steps

To 2,4-difluoro-phenylamine (1, 50.00 g, 0.39 mol) were added 550 mL of anhydrous dichloromethane, and anhydrous pyridine (61.27 g, 0.77 mol), followed by addition of benzyl chloroformate (2, 79.28 g, 0.46 mol) dropwise while maintaining the temperature at <30° C. The reaction mixture was stirred at room temperature for 2 hours and an additional 6.61 g (0.04 mol) of benzyl chloroformate was added and the reaction stirred an additional 2 hours, followed by addition of another 6.61 g of benzyl chloroformate. The reaction mixture was stirred overnight at room temperature, then concentrated under reduced pressure and diluted with 250 mL of water. The pH was adjusted to 2 with 2 M aqueous hydrochloric acid, then extracted with 3×250 mL of ethyl acetate. The organic layers were combined and dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The residue was slurried in hexane, filtered and the solid collected and dried to provide the desired compound (24, 78.6 g, 77%).

Provenance & Evidence