2-Fluoropyridine → Tert-butyl 4-cyano-4-(pyridin-2-YL)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 4-cyanopiperidine-1-carboxylate (220 mg, 1.05 mmol) and 2-fluoropyridine (0.094 mL, 1.10 mmol) was dissolved in 5.2 mL of THF. The reaction was purged with a stream of nitrogen and cooled to −78° C. To this reaction was added 1M sodium bis(trimethylsilyl)amide in THF (1.47 mL, 1.47 mmol), which was stirred for 1 hour. The reaction was warmed to ambient temperature, stirred for 1 hour, and quenched with a saturated ammonium chloride solution. The mixture was extracted with dichloromethane (3×10 mL). The combined organic extracts were dried over sodium sulfate, filtered, concentrated, and subjected to silica gel chromatography eluting with 0-20% EtOAc in hexanes. Collection of product containing fractions and removal of solvent yielded tert-butyl 4-cyano-4-pyridin-2-ylpiperidine-1-carboxylate.

Provenance & Evidence