A representative series of 5-(4-hydroxyphenyl)-2-azabicyclo[3.2.1]octanes was synthesized and evaluated in vitro, as well as in vivo, as potential analgetic agents. In general, moderate to good activity (19 twice as active as morphine) was observed in the phenylquinone writhing assay (PQW), while only marginal activity was detected by the tail-flick method. Compounds 19 and 18, being the most active in the PQW model, also demonstrated weak binding affinity for the opiate receptors labeled by [3H]naloxone in rat brain homogenates.

of 80% formic acid was stirred and heated to 50" for 24 hr. Another 5 ml of 30% HzOz was added and the heating and stirring were continued until an aliquot of the solution failed to give a positive Schiff test (another 24 hr). The volatile components were removed under reduced pressure and the residue was treated with 3.5 g (150 mmol) of LiOH in 35 ml of water. The resulting solution was heated in an autoclave at 120" for 12 hr. A white precipitate was isolated by filtration and washed with several portions of ethanol and then anhydrous ether. The resulting white powder was dried in uacuo to give 2.3 g (56%) of pure 4b. The observed spectral and physical properties were in agreement with those previously reported for this compound.3