Scalable Synthesis of (<i>R</i>,<i>R</i>)-<i>N</i>,<i>N</i>-Dibenzyl-2-fluorocyclohexan-1-amine with CsF under Hydrogen Bonding Phase-Transfer Catalysis

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 fluorination 200 g racemic trans-N,N-dibenzyl-2-bromocyclohexan-1-amine in mechanically stirred 1 L glass reactor using 0.5 mol % bis-urea organocatalyst. In these experiments, full conversions were obtained high mixing intensities (impeller average shear rate >10 000 s–1; maximum energy dissipation per unit mass >300 W/kg). The thermal safety reaction was assessed by differential scanning calorimetry calorimetry, assigning Stoessel’s critical class 3.