Continuous Safety Improvements to Avoid Runaway Reactions: The Case of a Chloro-Thiadiazole Intermediate Synthesis toward Timolol,Organic Process Research & Development

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Continuous Safety Improvements to Avoid Runaway Reactions: The Case of a Chloro-Thiadiazole Intermediate Synthesis toward Timolol
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2020-05-19 , DOI: 10.1021/acs.oprd.0c00048
Alessandro Agosti ₁ , Silvia Panzeri ₁ , Federico Gassa ₁ , Massimo Magnani ₁ , Giulia Forni ₁ , Marco Quaroni ₁ , Lazzaro Feliciani ₁ , Giorgio Bertolini ₁

Affiliation

Detailed process safety investigation of an old process revealed hidden, previously unnoticed danger. The synthesis of morpholine-adduct 2 was performed under reaction conditions very close to triggering a potentially dangerous runaway reaction. Process modifications such as dilution with an inert solvent allowed gaining better control of the process. Ultimately, improvement in both quality and yield was obtained.

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