Configurational Stability Racemization and Enantiomerization

Enantiomerization is promoted by the basic groups on the CSP and at a defined flow rate, with first-order kinetics and a ti/2 of approximately 14 and 22 min for the two enantiomers [14]. At first glance, it may seem surprising that two enantiomers interconvert with different rates. However, this is easily explainable by the chiral 

Low configurational stability is used in various inventive modes to recycle wrong enantiomers of intermediates for chiral drugs. Recycling of (3R)-6 into (35)-6 is an important aspect of the process for production of the target compotmd (35)-l, another example of which we shall consider in Chap. 7 (Sertraline). 

Compound (3S)-6 is a key building block for the 3-acylamino derivative 1, a highly potent y-secretase inhibitor for potential use in Alzheimer s disease. The structures of all the target compounds 1-3 are characterized by three stereogenic centres and an amide bond that coimects the 1,2-diaryl carboxylic acid subunits to the (3S)-NH2 group. On the other hand, target structure 4 lacks the two stereogenic centers in the carboxylic subtmit. 

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