Retrosynthetic Analysis of Fexofenadine

Despite the cost-benefit limitations to the development of a single-enantiomer drug, many original syntheses of pure enantiomers have been reported. Some of these are discussed in the following section, after a brief overview of non-stereoselective approaches. 

Each intermediate in retrosynthetic analysis is a new target molecule, and combination, in the last step, of the last two intermediates into the TM corresponds to highly convergent synthesis, the advantages of which, compared to consecutive synthesis, have been repeatedly discussed in textbooks on organic synthesis. 

Two synthons, cationic A and anionic B, which are the result of disconnection (a), have a couple of synthetic equivalents, for example, (1) and (2) in Table 10.3. 

Two synthons C and D are the result of an alternative disconnection b of the CH2-CH2Ar bond. Finally, retrosynthetic analysis c suggests two functional group interconversions followed by disconnection of the amide N-CO bond, affording synthons E and F. This analysis has been used in the synthesis of the sila-bioisostere of fexofenadine (49), as described in Sect. 10.4.3. 

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