The discovery of a new synthetic route to an API can show potential, but often it is either not economical or the reaction conditions are not practical for production scale.  Further development of reactions often results in the discovery of an additive which enhances the reaction and allows for better economic and acceptable reaction conditions.  Additives have long been used in organic chemistry as a means to tune both reactivity and selectivity.  The benefit of an additive in a reaction can be discovered as part of a well defined research proposal such as the intentional use of a Lewis acid as a coordinating additive.  On the other hand, beneficial additives can also be discovered by serendipity, such as a low level impurity in a starting material or a catalyst that enhances the key transformation in some way.  In these cases the chemist must design a plan to uncover the identity of this material, understand its function and apply it in a well controlled way.  The impact of an additive on the chemistry can make the difference between scalable and non-scalable processes.  This talk will detail two reactions that have benefited from the use of additives during development and their application to continuous process'.

Leveraging Lewis and Bronsted acid additives in process development

248th National Meeting (2014)

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