Dicyclohexylcarbodiimide → 4-[3-(4-Fluoro-phenoxy)-phenylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Steps

To a mixture of N-Boc piperidine-4-carboxylic acid (9.2 g, 0.04 mol) and DCC (dicyclohexylcarbodiimide) (8.2 g, 0.04 mol) in ethyl acetate (150 mL) was added HOAt (1-hydroxy-7-azabenzotriazole) (5.5 g, 0.04 mol) in DMF (dimethylformamide) (40 mL). The mixture was stirred at room temperature for 10 minutes and then 3-(4-fluoro-phenoxy)-phenylamine (8.7 g, 0.043 mol) in ethyl acetate (50 mL) was added. The reaction mixture was allowed to stir overnight at room temperature and then was concentrated to remove most of the ethyl acetate. The precipitated solid was removed by filtration through Celite. The filtrate was diluted with ethyl acetate and washed with 1 N HCl, saturated NaHCO3 and brine (3×60 mL). The organic phase was dried with MgSO4 and concentrated. The residue was purified on silica eluting with 20% ethyl acetate/hexanes to afford 4-[3-(4-fluoro-phenoxy)-phenylcarbamoyl]-piperidine-1-carboxylic acid tert-butyl ester (14.2 g, 86%) as an off-white solid.

Provenance & Evidence