A Baeyer−Villiger monooxygenase enzyme has been used to manufacture a chiral sulfoxide drug intermediate on a kilogram scale. This paper describes the evolution of the biocatalytic manufacturing process from the initial enzyme screen, development of a kilo lab process, to further optimization for plant scale manufacture. Efficient gas−liquid mass transfer of oxygen is key to obtaining a high yield.

An efficient route to AZD4635 has been developed utilizing the Suzuki−Miyaura reaction of a boronate ester prepared by C−H borylation on a multikilogram scale. Preparation of the cross-coupling partner using bromine/pyridine/ methanol has highlighted the incompatibility of this reagent/solvent combination with tantalum, which is commonly used in the construction and repair of standard manufacturing vessels.