A chiral synthesis of (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'- oxazolidin-2'-one]: a conformationally restricted analogue of acetylcholine that is a potent and selective alpha7 nicotinic receptor agonist.

A direct, short chiral synthesis of the selective alpha7 nicotinic receptor agonist (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one] (AR-R17779) is presented. The key step utilized attack of the dianion of the (R)-HYTRA ester [(R)-(+)-2-hydroxy-1,2,2-triphenylethyl acetate] on quinuclidin-3-one, followed by a selective precipitation of the diasteriomeric tertiary alcohol that led to (S)-(-)-AR-R17779 in two additional steps.