The Big Test Going to Plant Scale

Chemical synthesis can work beautifully on a small scale in the laboratory where the conditions can be meticulously controlled and the course of a reaction monitored in great detail, but it is not until a scale-up to the plant has been conducted that data on its robustness and sensitivity to various parameters will become obvious. Thus in parallel with the efforts put in to developing and optimizing the asymmetric step, comprehensive resources were invested in conducting trial runs on various scales in the pilot plant. A compilation of significant batches is shown in Tab. 1 together with conditions of operation and comments on the outcome. It is worth noting the increase in process performance quality over time as a result of development and optimizations exemplified, e.g., by a steady improvement in yield and % ee. 

Charged Sulfide 1.6 kg 1.6 kg 6.7 kg 104 kg Pyrmetazole (sulfide substrate used as base for calculation) 

Reaction Solvent for the oxidation EtOAc EtOAc Toluene Toluene  

Sulfone (HPLC) 3% 3.8% 1.6% 2.4% The only byproduct formed in signifi- 

Workup Precipitation of the racemate Yes Yes No No The crude product is dissolved in 

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