The synthesis of the d4-forms of rac- and R-lofexidine was accomplished. Two methods are described; one method is a two-step synthesis of rac-d4-lofexidine from 2-chloropropionitrile, the second method is a three-step preparation of R-d4-lofexidine in absolute enantiomeric purity from S-methyl lactate. The commercial availability of R-methyl lactate makes this latter enantioselective synthesis applicable also to the synthesis of S-d4- lofexidine. These procedures also conserve the utilization of the relatively expensive [1,1′,2,2′-2H 4]ethylene diamine precursor. The availability of S- and R-d 4-lofexidines will enable pharmacokinetic studies to be carried out to determine if differential in vivo metabolism of the two enantiomers of lofexidine occurs.
|Original language||English (US)|
|Number of pages||4|
|Journal||Journal of Labelled Compounds and Radiopharmaceuticals|
|State||Published - Aug 1 2009|