Ammonium Chloride → Tert-butyl 4-cyano-4-(cyclopropylmethyl)piperidine-1-carboxylate

Participants

Reaction Steps

A solution of tert-butyl 4-cyanopiperidine-1-carboxylate I-1 (1.0 g, 4.8 mmol) in THF (20 mL) at room temperature was treated with KHMDS (9.6 mL of a 1.0 M solution in TBF, 9.6 mmol). After 30 min, (bromomethyl)cyclopropane (0.47 mL, 4.8 mmol) was added dropwise and the mixture was stirred until LCMS indicated the reaction was complete. The reaction mixture was poured into saturated aqueous NH4Cl (50 nil) and extracted with EtOAc (3×50 mL), and the combined organic extracts were dried (Na2SO4) and concentrated under reduced pressure to afford tert-butyl 4-cyano-4-(cyclopropyl-methyl)piperidine-1-carboxylate (I-2, M+H+=265.2). This material was used in subsequent reactions without further purification.

Provenance & Evidence