Sodium hydride → HCID 58732860, compound

Participants

Reaction Steps

3-(3-Fluoro-5-nitro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. A 3 L 3-neck round bottom flask was charged with sodium hydride (60% in oil, 54.24 g, 1.356 mol) and DMF (1 L). The flask was cooled in an ice bath, a solution of (S)-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester alcohol (210 g, 1.043 mol) in DMF (500 mL) was added dropwise over 30 minutes to the flask, maintaining an internal temperature below 5° C. The solution was stirred for 1 hour, then was added via a canula into a 5 L 3-neck round bottom flask charged with a solution of 3,5-difluoronitrobenzene (169.25 g, 1.064 mol) that was cooled in an ice bath. The addition lasted for 1 hour, maintaining an internal temperature below 5° C. The reaction mixture was warmed to room temperature and stirred for 4 hours and diluted with 6 L ethyl acetate. The organic layer was washed with saturated ammonium chloride (4 L), sodium bicarbonate (2 L) and brine (2 L), dried (Na2SO4) and concentrated to afford the desired product (S)-3-(3-fluoro-5-nitro-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester as an syrup (360 g, purity ˜95%).

Provenance & Evidence