Phenylacetonitrile → 2-Phenyl-(3-pyridyl)-4-(2-azabicyclo[2.2.2]oct-2-yl)butyronitrile

Participants

Reaction Conditions

Reaction Steps

A mixture of 25 parts of benzyl cyanide, 35 parts of 3-bromopyridine and 220 parts of dry toluene is heated to 80° C. with stirring. Then, 19 parts of sodamide is added portionwise over a period of 1 hour while the temperature is maintained at 80°-85° C. with some cooling. The resultant mixture is heated to 105° C. and a solution of 56 parts of 2-(2-chloroethyl)-2-azabicyclo[2.2.2]octane in 220 parts of dry toluene is added portionwise. The mixture is then heated at 105°-110° C. for an additional 3 hours before it is cooled and 250 parts of water is added. The organic layer is separated and dried and the solvent is evaporated to leave a residue which is dissolved in ether and filtered. The ether solvent is evaporated from the filtrate and the residual oil is distilled under reduced pressure to provide 2-phenyl-2-(3-pyridyl)-4-(2-azabicyclo[2.2.2]oct-2-yl)butyronitrile. Alternately α-phenyl-3-pyridylacetonitrile (U.S. Pat. No. 3,225,054) is reacted with 2-(2-chloroethyl)-2-azabicyclo[2.2.2]octane directly.

Provenance & Evidence