3-PPP (N-n-propyl-3-(3-hydroxyphenyl)piperidine) is a mixed sigma ÃÂ<sub>1</sub> and ÃÂ<sub>2</sub> receptor agonist (with similar affinity for both subtypes, though slightly higher affinity for the latter) and D<sub>2</sub> receptor partial agonist which is used in scientific research. It shows stereoselectivity in its pharmacodynamics. (+)-3-PPP is the enantiomer that acts as an agonist of the sigma receptors; it is also an agonist of both D<sub>2</sub> presynaptic and postsynaptic receptors. Conversely, (âÂÂ)-3-PPP, also known as preclamol (), acts as an agonist of presynaptic D<sub>2</sub> receptors but as an antagonist of postsynaptic D<sub>2</sub> receptors, and has antipsychotic effects. 3-PPP has also been reported to be a monoamine reuptake inhibitor and possibly to act at adrenergic receptors or some other non-sigma receptor.
The Grignard reagent was prepared for 3-Bromoanisole [2398-37-0] (1) and this was reacted with 3-Bromopyridine [626-55-1] (2) to give 3-(3-methoxyphenyl)pyridine [4373-67-5] (3). Reaction with 1-bromopropane [106-94-5] occurred to give the quaternary salt PC13695099 (4a). {Alternatively catalytic hydrogenation of 3 could be attempted directly to give 3-(3-methoxyphenyl)piperidine [79601-21-1] (4b). A second reductive amination with propionic acid was then performed.} Catalytic hydrogenation of the quat cation gave 3-(3-methoxyphenyl)-1-propylpiperidine [86562-23-4] (5). Demethylation with hydrogen bromide then completed the synthesis of preclamol (6).