Methyl iodide → tert-Butyl 4-cyano-4-methylpiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

In a round-bottomed flask, tert-butyl 4-cyanopiperidine-1-carboxylate (0.70 g, 3.3 mmol) was dissolved in THF (14 mL). The solution was cooled to −76° C. and lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 3.7 mL, 3.7 mmol) was added dropwise over 15 min. The yellow solution was stirred at −76° C. for 30 min then iodomethane (0.32 mL, 5.1 mmol) was slowly added. The reaction mixture was stirred at −76° C. for 30 min and then warmed to room temperature over 1 h. The reaction mixture was quenched with 10 mL saturated aqueous NH4Cl, diluted with water and extracted with EtOAc (2×). The organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by SiO2 chromatography with 0% to 20% EtOAc/hexanes to afford 0.71 g (95%) of 4-cyano-4-methyl-piperidine-1-carboxylic acid tert-butyl ester as a pale yellow oil.

Provenance & Evidence