Bis(2-chloroethyl)amine → 4-(4-Chlorophenyl)piperidine-4-carbonitrile

Participants

Reaction Conditions

Reaction Steps

49 g 4-chlorobenzyl cyanide 1 (323 mmol, 1.00 equiv) and 58 g of bis[2-chloroethyl]amine (323 mmol, 1.00 equiv) were dissolved in 325 mL of anhydrous DMF in a 2 L round bottom flask fitted with a magnetic stir bar, reflux condenser, and N2 inlet. The mixture was cooled in an ice water bath, then 52 g of 60% NaH in mineral oil (1293 mmol, 4.00 equiv) was added to the stirring solution at a rate such that the exothermic reaction did not become violent. After the addition was complete, the apparatus was transferred to an oil bath and the mixture heated to 60° C. and stirred for 48 h under N2 atmosphere. The mixture was cooled to room temperature and the remaining hydride carefully quenched under N2 by dropwise addition of a small amount of H2O. The resultant slurry was poured into 2 L of rapidly stirring H2O and the pH adjusted to ˜1 with concentrated HCl. The mixture was transferred to a 4L separatory funnel and extracted with 3×500 mL of hexane. The organic extracts were discarded and the aqueous extracts was adjusted pH to ˜9 by the addition of solid K2CO3. The resultant precipitate was collected by vacuum filtration and washed with small portions of H2O, followed by hexane. The tan solid was dried under vacuum to yield 4-(4-chloro-phenyl)-piperidine-4-carbonitrile: MS (ES) M+H expected=221.7, found=221.1.

Provenance & Evidence