In the last two decades a series of highly potent, orally bioavailable viral protease inhibitors have gained approval for HIV treatment. Viral protease inhibitors, such as Atazanvir and Saquinavir are listed by the World Health Organization as essential medicines for a basic health care system. Most of the approved HIV protease inhibitors contain a chiral aminoalcohol structure in the central core. In this presentation the three step continuous flow synthesis of the chiral aminoalcohol motif required for the preparation of Atazanavir will be described. This requires the continuous generation of anhydrous diazomethane from the respective amino acid. Diazomethane is a volatile, highly irritating, poisonous and carcinogenic compound and furthermore is exceedingly heat-, light- and shock sensitive and tends to decompose explosively. A safe continuous strategy that relies on membrane separation technology for the preparation of anhydrous diazomethane will be described in this presentation.

Continuous flow generation and reactions of anhydrous diazomethane: Toward the continuous manufacturing of the HIV protrease inhibitor Atazanavir

248th National Meeting (2014)

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