Large-Scale Amidations in Process Chemistry: Practical Considerations for Reagent Selection and Reaction Execution

This review describes the practical aspects involved in the implementation of large-scale amidations in process chemistry. Coupling reagent, base, additive, and solvent selections are critically analyzed to highlight their pros and cons. Other important factors to be considered on large scale, such as atom economy, cost, safety, and toxicity, are also examined. These concepts are then showcased through selected examples from the literature for the synthesis of active pharmaceutical ingredients.