Toluene → tert-Butyl 4-cyano-4-(morpholin-4-ylcarbonyl)piperidine-1-carboxylate

Participants

Reaction Steps

To a solution of tert-butyl 4-cyanopiperidine-1-carboxylate (9.46 g, 45 mmole) in dry THF (60 mL) was added 0.5M solution of KHMDS in toluene (100 Ml, 50 mmole) at −78° C. under argon with stirring. After addition of KHMDS, the reaction mixture was stirred for 1 h at −78° C. After this time, morpholine-4-carbonyl chloride (7.48 g, 50 mmole) was added. The resultant reaction mixture was stirred for 1 h at −78° C. and then 1 h at room temperature. The reaction mixture was then treated with cooled 1N NaOH (80 mL) and extracted with EtOAc (2×350 mL). The combined organic extracts were washed with brine (2×100 mL), dried over MgSO4, filtered, and concentrated to afford the title compound (I-2) as a white solid. This product was used in next step without further purification. Analytical LCMS: single peak (214 nm), 2.799 min.

Provenance & Evidence