4-Fluorobenzonitrile → tert-Butyl 4-(4-cyanophenoxy)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

Add a solution of N-Boc-4-hydroxypiperidine (3.0 g, 14.9 mmol) in DMF (5 mL) to a suspension of sodium hydride (894 mg, 22.4 mmol) in DMF (17 mL). Stir the reaction mixture while heating at 50° C. for 45 min. Then add a solution of 4-fluoro-benzonitrile (2.16 g, 17.9 mmol) in DMF (5 mL). Stir and heat at 50° C. for 2 h. Let cool to room temperature and quench with water (0.5 mL). Evaporate DMF. Redissolved the resulting residue in EtOAc/hexanes (2/1, 20 mL) and wash with water (3×15 mL). Dry the organic layer over magnesium sulfate, filter and concentrate. Purify by chromatography (EtOAc/hexanes 20% and EtOAc/hexanes 10%) to yield the title compound (2.32 g, 52%).

Provenance & Evidence