A CHIRAL SYNTHESIS OF DAPOXETINE HYDROCHLORIDE, A SEROTONIN REUPTAKE INHIBITOR, AND ITS C-14 ISOTOPOMER

The C-14-isotopomer of dapoxetine-[C-14] HCl (S (+)-N,N-dimethyl-alpha-[2-(1-naphthalenyloxy) ethyl-2-C-14]benzenemethanamine hydrochloride, 1a), a potent serotonin re-uptake inhibitor has been prepared by a chiral synthesis, starting with tert.-butyloxyphenylglycine (3). Borane reduction, followed by activation of the resulting alcohol 4 as its mesylate 5b, provided the chiral starting material. The radiolabel was introduced by reaction of 5b with sodium cyanide-[C-14]. The desired product (1) was then elaborated from nitrile 6a,b via a five step synthesis in an overall 19.5% radiochemical yield.