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Continuous multi-step synthesis of fine chemicals

By Tetsuo Satoh |

Currently, the active components of most pharmaceuticals and fine chemicals are synthesized by multiple batch reactions, in which all starting materials are mixed in reaction vessels and the desired compounds are extracted and purified after each reaction has finished. Such methods require excess energy and many operational steps, and often generate a significant amount of waste. Although continuous flow reactors have advantages over batch reactors, it has been difficult to adopt the technology for complex, multi-step reactions. Now, professor Shu Kobayashi and his research group at the University of Tokyo (Tokyo, www.u-tokyo.ac.jp) have developed highly active, immobilized heterogeneous catalysts for column reactors, which enables the multi-step synthesis of pharmaceuticals. The researchers have demonstrated the continuous flow reactors for the eight-step production process (diagram) of (R)-rolipram, an anti-inflammatory drug. The complete synthesis did not require the isolation or purification of intermediates or the purification of products from catalysts. By simply replacing a column packed with a chiral heterogeneous catalyst with another column packed with the opposing enantiomer, the researchers were able to produce (S)-rolipram. “This…
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