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Download fileScalable Synthesis of (R,R)‑N,N‑Dibenzyl-2-fluorocyclohexan-1-amine with CsF under Hydrogen Bonding Phase-Transfer Catalysis
journal contribution
posted on 2021-12-03, 13:41 authored by Anna Chiara Vicini, Diké-Michel Alozie, Philippe Courtes, Giulia Roagna, Catherine Aubert, Victor Certal, Youssef El-Ahmad, Sébastien Roy, Véronique GouverneurHydrogen bonding phase-transfer catalysis
offers a convenient solution
to activate safe and economical metal alkali fluorides for enantioselective
nucleophilic fluorination. Herein, we demonstrate the scalability
of this protocol with the fluorination of 200 g of racemic trans-N,N-dibenzyl-2-bromocyclohexan-1-amine
in a mechanically stirred 1 L glass reactor using 0.5 mol % of a bis-urea
organocatalyst. In these experiments, full conversions were obtained
for high mixing intensities (impeller average shear rate >10 000
s–1; maximum energy dissipation per unit of mass
>300
W/kg). The thermal safety of the reaction was assessed by differential
scanning calorimetry and reaction calorimetry, assigning the reaction
to Stoessel’s critical class 3.
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transfer catalysis offershydrogen bonding phasehigh mixing intensitiescritical class 3differential scanning calorimetryenantioselective nucleophilic fluorinationurea organocatalysttrans </thermal safetystoessel ’scalable synthesisreaction calorimetryr </n </kg ).full conversionsconvenient solutionactivate safe>‑ dibenzyl>- dibenzyl5 mol300 w200 g10 000