Journal
ORGANIC PROCESS RESEARCH & DEVELOPMENT
Volume 26, Issue 6, Pages 1562-1689Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.oprd.2c00005
Keywords
large-scale; process chemistry; active pharmaceutical ingredient; amidation
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This review provides a description of the practical aspects of implementing large-scale amidations in process chemistry. It critically analyzes the selection of coupling reagents, bases, additives, and solvents to highlight their advantages and disadvantages. Other important factors such as atom economy, cost, safety, and toxicity are also examined in the context of large-scale applications. Selected examples from the literature showcasing these concepts in the synthesis of active pharmaceutical ingredients are included.
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.
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