Donald W. Kessler

Rapid access to enantiopure bupropion and its major metabolite by stereospecific nucleophilic substitution on an α-ketotriflate

Abstract A stereospecific method for the synthesis of enantiopure α-aminoketone from its corresponding α-hydroxy-ketone via the triflate intermediate is discussed. This strategy provides a rapid and efficient route for the preparation of either enantiomer of bupropion and its biologically active hydroxylated metabolite.

Pd-catalyzed aminations of aryl triazolones: Effective synthesis of hydroxyitraconazole enantiomers

Abstract A palladium-catalyzed amination of triazolone 3 by piperazine 2 was used as the key step in an efficient synthesis of highly enantiomerically-pure hydroxyitraconazole isomers. Compound 2 (>99%ee) was prepared by reaction of an achiral phenol precursor with the corresponding dioxolyl tosylate (>99% ee), and 3 was made by alkylation of 6 with 7 (>99%ee).

Practical chemical and enzymatic technologies for (S)-1,4-benzodioxan-2-carboxypiperizine intermediate in the synthesis of (S)-doxazosin mesylate

Abstract ( S )-1,4-Benzodioxan-2-carboxypiperazine ( S )- 2 , the key chiral intermediate for the synthesis of ( S )-doxazosin, was prepared utilizing two approaches: (i) enzymatic resolution of ethyl 1,4-benzodioxan-2-carboxylate with an esterase ( Serratia ) followed by amide formation; (ii) direct resolution of 1,4-benzodioxan-2-carboxypiperazine 2 with d -tartaric acid. An efficient process for the conversion of ( S )- 2 to ( S )-doxazosin mesylate was developed (80% yield, 99.9% e.e.).