Diastereo-isomeric crystallization

For the preparation of optically active material the intermediate vinyl ketone (2) was condensed with (—)-a-phenethylamine and the resulting diastereo-isomeric Mannich base (3) [(— )-a-phenethylamine instead of diethyl] was separated by fractional crystallization of its oxalate salt. The above synthetic scheme was then applied to the separate optically active vinyl ketones (or their derivatives). 

The synthesis of folinic acid from fohc acid creates a new asymmetric center at the 6-carbon, and both diastereoisomeric forms tend to crystallize together. Crystallization of the calcium salU from water gives the ZL-form which is about twice as active biologically as the original mixed crystals, and upon conversion to formylfolic acid it does not increase in foUc-like activity for L. casei as does the diastereoisomeric mixture. This /L-diastereo-isomeric form appears to be identical with natural folinic acid. ... 

A novel application of this chemistry to a short synthesis of enantiomeri-cally pure 2-hydroxymorpholine 136, an intermediate in the synthesis of the substance P antagonist Apprepitant 138 (Scheme 7.18), was reported by a group from Merck [64]. Interestingly, despite the initial formation of a complex diastereo-meric mixture, compound 136 was isolated in high yield and enantioselectivity via a crystallization-induced diastereoselection and could be completely isomerized to 137, a precursor to 138. 

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