| 摘要 |
Processes and intermediates for preparing 2-substituted piperidines such as 2- substituted d-threo piperidines are provided. In preferred embodiments, the processes of the invention comprise the steps of reacting a 2-substituted pyridine with hydrogen in the presence of a catalyst in an alkanoic acid, an d adding an alkyl alkanoate to the resulting mixture of threo and erythro 2- piperidine stereoisomers to precipitate alkanoate salts of the erythro stereoisomers preferentially with respect to alkanoate salts of the threo stereoisomers. The erythro salts thenare reacted with aqueous base to form t he corresponding mixture of erythro amide free bases, which are reacted with a suitable organic acid resolving agent in an alkyl alcohol solvent to form ac id salts of the l-erythro stereoisomers preferentially with respect to the d- erythro stereoisomers. The l-erythro acid salts are then reacted with aqueou s base to form the l-erythro piperidine amide free base which, in turn, is epimerized to produce the desired d-threo product by treating it in an organ ic solvent with an alkali metal alkoxide.
|
