Citric Acid → (E)-3-(3-dimethylamino-1-propenyl)-1-(2-phenoxyethyl)piperidine dicitrate

Participants

Reaction Conditions

Reaction Steps

n-Butyllithium (4.1 ml, 2.5M solution in hexanes) was added to a mixture of 2-dimethylaminoethyl triphenylphosphonium bromide (4.71 g) in dry THF (50 ml) with stirring at 0° C. under nitrogen. The mixture was stirred at 0° C. for 30 minutes and then a solution of N-(2-phenoxyethyl)piperidine-3-carbaldehyde (2.41 g) in THF (5 ml) was added dropwise at 0° C. with stirring. The mixture was allowed to warm to ambient temperature and then boiled under reflux for 18 hours under nitrogen. The mixture was evaporated to dryness under reduced pressure and then treated with dilute hydrochloric acid. The mixture was washed with dichloromethane, basified with 2M sodium hydroxide solution and extracted with dichloromethane to give an oil. The oil was triturated with petroleum ether b.p. 40°-60° C., and the supernatant petroleum ether decanted off to leave an oil. The oil was stored at 5° C. for 64 hours, during which time a fine crystalline solid formed. Petroleum ether b.p. 40°-60° C. was added and the mixture was filtered to give a solid which was discarded. The filtrate was evaporated to yield a pale yellow oil, which was identified as (E)-3-(3-dimethylamino-1-propenyl)-1-(2-phenoxyethyl)piperidine. A portion of this oil (2.0 g) was dissolved in ether and acidified with ethereal citric acid to give a precipitate which was collected by filtration, washed with acetone and dried to give (E)-3-(3-dimethylamino-1-propenyl)-1-(2-phenoxyethyl)piperidine dicitrate, m.p. 65°-70° C.

Provenance & Evidence