Hydrogen Cyanide → 3-Methyl-1-phenyl-1,3,7-triaza-spiro[4.5]decan-4-one

Participants

Reaction Steps

A solution comprising of 3-Oxo-piperidine-1-carboxylic acid tert-butyl ester (2.5 g, 12.55 mol) and aniline (1.28 g, 13.8 mmol) in acetic acid (10 ml) was stirred at RT for 60 mins under nitrogen. Trimethylsilyl cyanide (1.57 ml, 12.55 mmol) was added carefully into the reaction mixture. The reaction mixture was left to stir at RT for a further 90 mins. The reaction mixture was cannulated into a rapidly stirring flask containing crushed ice (50 ml) and concentrated ammonium hydroxide (30 ml) for 10 minutes, resulting in a precipitate. This solution was allowed to stir for a further 15 mins to ensure no HCN remained before adding EtOAc (150 ml) to dissolve the precipitate. The organics were then separated and the aqueous washed with a further EtOAc (50 ml). The organics portions were combined, washed with brine (100 ml), dried (MgSO4) and concentrated in vacuo to afford an oil. Purification of the crude product by chromatography on silica eluting with 0-50% EtOAc in iso-hexane afforded the title compound.

Provenance & Evidence