Water → (R)-tert-butyl 3-((3-chloropyridin-2-yl)amino)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-bromo-3-chloropyridine (203.8 g, 1.06 moles), sodium tert-amylate (147 g, 1.27 moles), tert-butyl (3R)-3-aminopiperidine-1-carboxylate (249.5 g, 1.25 moles) in toluene (2 L) was heated to 80° C. To this solution was added chloro(di-2-norbornylphosphino)(2-dimethylaminoferrocen-1-yl) palladium (II) (6.1 g, 10.06 mmol) followed by heating to 105° C. and holding for 3 h. The reaction mixture was cooled to room temperature, 1 L of water was added, then the biphasic mixture was filtered through Celite®. After layer separation, the organic phase was washed with 1 L of water followed by treatment with 60 g of Darco® G-60 at 50° C. The mixture was filtered through Celite®, and concentrated to a final total volume 450 mL, resulting in the precipitation of solids. To the slurry of solids was added 1 L of heptane. The solids were collected via filtration and then dried to afford the title compound as a dull orange solid (240.9 g, 73% yield).

Provenance & Evidence