Tert-butyl 4-cyanopiperidine-1-carboxylate → Tert-butyl 4-cyano-4-(4-methylpyridin-2-yl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 4-cyanopiperidine-1-carboxylate (15.2 g, 72.3 mmol) and 2-fluoro-4-methylpyridine (9.64 g, 87.0 mmol) was dissolved in 361 mL of THF. The reaction was purged with a stream of nitrogen and cooled to −78° C. To this reaction was added 1.0 M sodium bis(trimethylsilyl)amide in THF (101 mL, 101 mmol), which was stirred for 1 hour. The reaction was warmed to ambient temperature, stirred for 36 hours, and quenched with a saturated ammonium chloride solution. The mixture was extracted with dichloromethane (3×200 mL). The combined organic extracts were dried over sodium sulfate, filtered, concentrated, and subjected to silica gel chromatography eluting with 0-25% EtOAc in hexanes to yield tert-butyl 4-cyano-4-(4-methylpyridin-2-yl)piperidine-1-carboxylate.

Provenance & Evidence