| 摘要 |
A process is disclosed for the production of a product which is enriched in a desired enantiomer of a phenylpropionic acid selected from ibuprofen and flurbiprofen, or their pharmaceutically acceptable salts, which ccomprises the following stagles: (a) a resolution stage, in which an ?-methylcenzylamine salt of the phenylpropionic acid is prepared which is erriched in the desired enantiomer by contacting, in a mixture of toluene and memanol as solvent, a substantially racemic mixture of the phenylpropionic acid with an anantiomer of ?methylbenzylamine, the respective molar ratio of the susbtantially racemic phenylpropionic acid to the ?-methylbenzylamine being in me range of about 1:0.25 to about 1:1; (b) a recrystallisation stage, in which the resulting enriched salt is recrystallised from a mixture of methanol and toluene to give an ?-methylbenzylamine salt of the phenylpropionic acid which is further enrichcd in the desired enantiomer; (c) an optional liberation stage, in which the phenylpropionic acid which is further enriched in the desired enantiomer is liberated from the recrystallised salt; (d) an optional salt-preparation stage in which a solid salt of the phenylpropionic acid further enriched in me desired enantiomer is isolated, me solid salt optionally being even further enantiomerically enriched in me desired enantiomer. The desired enantiomer is preferably the (S)-enantiomer, preferred salts are the ?-methylbenzylamine, lysine and sodium salts.
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