3-Quinuclidinol, (-)- → 1-Phenyl-cycloheptanecarboxylic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

Participants

Reaction Steps

A solution of (R)-(3)-quinuclidinol (10.13 g) and 1-phenyl-cycloheptanecarboxylic acid methyl ester (Example 14d) (9.25 g) in toluene (90 mL) was heated to reflux with a Dean-Stark trap for 30 min. The reaction mixture was allowed to cool to room temperature and the trap was removed. Sodium hydride (60% dispersion in mineral oil) (3.19 g) was added portionwise under nitrogen and the reaction mixture was heated to reflux overnight under nitrogen. The reaction mixture was cooled in an ice bath and diluted with ethyl acetate (200 mL) and water (200 mL). The mixture was filtered and the layers separated. The aqueous layer was extracted with ethyl acetate (2×250 mL) and the combined organic layers were washed with brine, dried over magnesium sulfate and evaporated to give the crude product which was purified by silica gel chromatography eluting with EtOAc containing 1% triethylamine to give the sub-titled compound as a colourless oil (7.63 g)

Provenance & Evidence