| 摘要 |
This invention concerns a new process of preparing cisapride, and the pharmaceutically acceptable acid addition salts thereof, by reductively aminating 1-¢3-(4-fluorophenoxy)-propyl!-3-methoxy-4-piperidinone in the presence of benzylamine under hydrogen in a reaction-inert solvent, yielding 1¢3-(4-fluorophenoxy)-propyl!-3-methoxy-4-piperidinamine having a cis/trans ratio of about 93/7, which is enriched in the amount of cis-stereoisomer by converting it into its acid addition salt, by treatment with a suitable inorganic acid, in an appropriate solvent, subsequent crystallisation and conversion to its free base form by treatment with an appropriate base, yielding 1-¢3-(4-fluorophenoxy)-propyl!-3-methoxy-4-piperidinamine having a cis/trans ratio of equal to or higher than 98/2. Subsequently, cis-¢3-(4-fluorophenoxy)-propyl!-3-methoxy-4-piperidinamine is reacted with the mixed anhydride of 4-amino-5-chloro-2-methoxy-benzoic acid and ethyl chloroformate in a reaction-inert solvent yielding cisapride.
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