Piperidine → HCID 853659, compound

Participants

Reaction Steps

A solution of 18.62 g of piperidine (0.219 mol) in 360 ml of hexane is admixed dropwise with 23.8 g of cyclohexyl isocyanate (0.190 mol) and then the cloudy mixture is heated at reflux for 2 hours, after which it is cooled and filtered to give 39.3 g of pure N-cyclohexylpiperidine-1-carboxamide (98.3% yield). A suspension of 15.05 g of this pure product (71.6 mmol) in 65 ml of dry toluene is admixed with 12 g of POCl3 (78 mmol) over 1 hour, and then, after a number of hours at 20° C., 18.1 g of N-butyl-N-ethylamine (0.179 mmol) are added over 2 hours, and then, after a further 2 hours at 20° C., 50 ml of water are added. 49 g of 35% sodium hydroxide solution are then added with cooling, after which the two-phase mixture is extracted with diisopropyl ether. Following drying and evaporation to dryness, the oil obtained, 20 g, is distilled at 185° C. under 1 mbar to give 17 g of the expected guanidine (81% yield).

Provenance & Evidence