PHOTOCHEMISTRY
‣ chemical engineers and both internal and external contractors . This later became our patented Iris Lab and Iris Max production platforms .* The Iris reactor platform is designed with the goal of kilos-to-tonnes production in mind . It is a wellcharacterised , LED lighting-based technology , featuring highly intensive and tunable photons at the reactor surface ( 0 ~ 0.5 W / cm 2 ). Reaction temperatures are adjustable , based on recirculative TCU liquid cooling / heating . Currently , four different wavelength models are available off the shelf ( 365 , 385 , 405 , 460 nm ). The 100W lab-scale system enables us to perform continuous variable reaction optimisation using DoE methods . The reaction conditions from Iris Lab are fully translatable in the 5 kW Iris Max for production with minimal amount of scale-up development .
Case study
Earlier this year , Snapdragon completed a groundbreaking photochemistry campaign for cGMP API manufacturing , making nearly 18 kg of the product with a single 5 kW Iris Max photoreactor . Making this drug for the first time in this quantity is extremely enabling and will help provide the proof many clients need to see photochemistry as efficient , reliable and powerful . The process in question involves an achiral trans-alkene isomerisation using blue light ( 440 ~ 460 nm ) to form cis-alkene intermediate , which can be subsequently transformed by a chiral catalyst ( no light needed ) selectively into a single chiral product ( proprietary structure ). The proprietary starting material is high-value and difficult to make .
Snapdragon recently made nearly 18 kg of API product using a single 5 kW Iris Max photoreactor '
Under thermal reaction conditions , a 50 / 50 mixture of the racemic product can be prepared , which requires tedious chiral chromatographic separation with a maximal theoretical yield of 50 % for the desired antipole product . Under the photochemical conditions , by contrast , the product was formed in > 80 % chemical yield and an optical purity of about 94 % ee . The optically pure product ( 99.8 ~ 99.9 % ee ) was then obtained by simple crystallisation with an overall isolated yield of > 70 % ( Figure 3 ). The scale-up process was performed in Snapdragon ’ s kilo lab fumehood under cGMP . With Snapdragon ’ s LabOS software automation control , aided by safety sensors and PLC safety interlocks , the flow process was able to reach an average substrate consumption rate of about 100 g / hour , to process about 30 kg of the product over a 300- hour operation .
The automation control system we created allowed us to monitor the process and run the production around the clock unattended . The team was able to watch it remotely and incorporated the ability to shut the system down if any critical safety control parameters fell out of range . Thankfully , we never ran into any hazardous situations that would have triggered the safety controls .
Outlook
The on-demand nature of photons makes them extremely attractive as an unorthodox class of reagents , thereby potentially providing supply chain resilience in the post-COVID world . This is especially exciting when photochemical processes can save multiple synthetic steps , making manufacturing production greener and economically more attractive . •
* - IRIS LAB and IRIS MAX are registered trademarks of Snapdragon Chemistry
Eric Fang
CHIEF SCIENTIFIC OFFICER
Figure 3 - Photochemical isomerisation of a Trans-alkene into a Cis-alkene
SNAPDRAGON CHEMISTRY k + 1 877 695 8363 J eric . fang @ snapdragonchemistry . com j www . snapdragonchemistry . com
60 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981