American Chemical Society
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

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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 Gouverneur
Hydrogen 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.