Guided optimization of a crystallization-induced diastereomer transformation to access a key navoximod intermediate

The recently reported crystallization-induced diastereomer transformation (CIDT) of a precursor to navoximod was investigated using online HPLC via a modified EasySampler probe that enables selective solution phase sampling of heterogeneous reaction mixtures. By employing both chiral and achiral stationary phases, the effects of time, temperature and equivalents of chiral resolving agent on the reaction yield and e.e. were interrogated. An inline racemization approach was applied after the CIDT and selective racemization over decomposition was demonstrated.