op1c00312_si_001.pdf (2.85 MB)
Scalable 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.
History
Usage metrics
Categories
Keywords
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