Formamide

Grabato, Jeb Reece H.; Federico, Sofia Angela P.; Hizon-Fradejas, Amelia B.; Mojica, Elmer-Rico E.

doi:10.1016/b978-0-12-824315-2.00949-0

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2024

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“…Through the judicious choice of solvent, product inhibition could be overcome using formamide as a solvent (Figure ). Although this synthetic challenge was successfully addressed, there were lingering concerns about the long-term manufacturing risks associated with the use of formamide in the process stemming from its toxicity, impurity profile risks, insufficient removal in the drying unit operation, and restrictions under REACH …”

Section: Resultsmentioning

confidence: 99%

Evolution of a Green and Sustainable Manufacturing Process for Belzutifan: Part 6─Development of a Nucleophilic Aromatic Substitution in Water

Le,

Wright,

Alwedi

et al. 2024

Org. Process Res. Dev.

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A convergent nucleophilic aromatic substitution (S N Ar) was developed as the final step in an improved manufacturing process to belzutifan. The reaction was performed in water to enable a reactive crystallization and direct isolation of the drug substance toward a green and sustainable process. Due to reaction sensitivity to the vapor phase composition, engineering controls around the headspace pressure and sweep rate were tuned to balance reactivity and selectivity to maximize product yield and purity. Ultimately, our investigation resulted in a robust process, which was successfully demonstrated at pilot plant scale.

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Section: Resultsmentioning

confidence: 99%