Continuous Ozonolysis Reaction to Produce 4AA
Abstract: Asymchem successfully implemented an industrial scale continuous Ozonolysis process to manufacture 4-Acetoxy-2-Azetidinone (4AA). The adopted system is capable of processing 120kg of starting material (SM) per day to produce multi-ton quantities of product per year. The continuous process provides several advantages (greener, safer, higher throughput and less space required at the manufacturing site) over the batch process, making it very attractive for manufacturing. This poster describes the Ozonolysis process and the different advantages it has to speed up and secure material delivery.
Description: Continuous Manufacturing (CM) has been successfully implemented at Asymchem for the past 4 years to produce active pharmaceutical ingredients (API) or their intermediates at industrial scale. A continuous Ozonolysis process is currently used to produce 4-Acetoxy-2-Azetidinone (4AA), a heterocyclic synthon for anti-inflammatory and antibiotic agents; see Figure 1.
The system consists of a customized countercurrent temperature controlled packed column where Ozone (O3) bubbles from the bottom and Substrate flows from the top (see Figure 2). The product is collected from the bottom of the column and any reacted/unreacted gas leaves on the top side.
The column has the capacity to process 120kg of starting material (SM) per day or generate 20 metric tons (MT) of product per year. Asymchem decided to run this process in continuous mode rather than batch due to the different advantages it poses: greener, safer, higher material throughput per unit volume and occupies less space.
- Green Process: Less frequent startups and shutdowns allow a reduction in the solvent/gas usage and subsequent generation of waste. Also, the tail or excess gas (O3/O2) is collected and reused for oxidation of organics at the site's waste water treatment plant.
- Safer: The residual volume in the packed column, at any point in time, is approximately 16 liters; this is significantly less residual volume when compared to its equivalent in batch (i.e. 1,000 liters). As such, less material (SM or product) is at risk when running the process in flow mode.
- Higher conversion and throughput per unit volume - The use of special packing increases the surface area and mass transfer between the gas & liquid media, this enhances the conversion of SM in less time. Due to its continuous nature (operating at steady state), the Ozonolysis system can process 63% more material per unit volume than the batch process.
- Less space at plant site: The Ozonolysis column occupies approximately 8 times less plant space than the equivalent batch reactor.
The manufacturing of 4AA, using a continuous platform, provided significant benefits compared to its homologous in batch mode. Producing more material in less amount of time and using less space made this process attractive to do it in flow mode. Asymchem constantly evaluates and adopts CM opportunities to make more efficient processes
Category: Drug Substance
Type: Small Molecules
Contact: Jordi Robinson ([email protected])