As reported in the October 2019 PTC Catalyst of the Month, tribenzyloxybenzyl quininium chloride worked better than 15 other chiral PTC quats screened for the reaction shown in the figure. A new patent was just issued that focuses on obtaining the desired polymorph of the product (S)-afoxolaner by recrystallization. In order to conduct this study, the inventors needed significant amounts of the product, so they successfully scaled up the chiral PTC addition of hydroxylamine to the substrate on a 1 kg scale.
Comparing the procedures from the two patents, it is apparent that some process improvement was performed, including reducing the amount of hydroxylamine from 3.0 equiv to 1.1 equiv and reducing the amount of solvent used from 30X to 9X.
If your company wants to improve performance by choosing the best phase-transfer catalyst for reactivity, selectivity, minimizing waste and achieving effective separation of the phase-transfer catalyst from the product, now contact Marc Halpern of PTC Organics.
About Marc Halpern
Dr. Halpern is founder and president of PTC Organics, Inc., the only company dedicated exclusively to developing low-cost high-performance green chemistry processes for the manufacture of organic chemicals using Phase Transfer Catalysis. Dr. Halpern has innovated PTC breakthroughs for pharmaceuticals, agrochemicals, petrochemicals, monomers, polymers, flavors & fragrances, dyes & pigments and solvents. Dr. Halpern has provided PTC services on-site at more than 260 industrial process R&D departments in 37 countries and has helped chemical companies save > $200 million. Dr. Halpern co-authored five books including the best-selling “Phase-Transfer Catalysis: Fundamentals, Applications and Industrial Perspectives” and has presented the 2-day course “Practical Phase-Transfer Catalysis” at 50 locations in the US, Europe and Asia.
Dr. Halpern founded the journal “Industrial Phase-Transfer Catalysis” and “The PTC Tip of the Month” enjoyed by 2,100 qualified subscribers, now beyond 130 issues. In 2014, Dr. Halpern is celebrating his 30th year in the chemical industry, including serving as a process chemist at Dow Chemical, a supervisor of process chemistry at ICI, Director of R&D at Sybron Chemicals and founder and president of PTC Organics Inc. (15 years) and PTC Communications Inc. (20 years). Dr. Halpern also co-founded PTC Interface Inc. in 1989 and PTC Value Recovery Inc. in 1999. His academic breakthroughs include the PTC pKa Guidelines, the q-value for quat accessibility and he has achieved industrial PTC breakthroughs for a dozen strong base reactions as well as esterifications, transesterifications, epoxidations and chloromethylations plus contributed to more than 100 other industrial PTC process development projects.
Dr. Halpern has dedicated his adult life to his family and to phase-transfer catalysis (in that order!).
