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SELECTBIO Conferences Flow Chemistry Asia 2019

Sándor B. Ötvös's Biography



Sándor B. Ötvös, Researcher, Institute of Chemistry, University of Graz

Sándor studied Chemistry at the University of Szeged (Hungary), and obtained his M.Sc. in 2009. He earned Ph.D. in 2013 at the same university (at Institute of Pharmaceutical Chemistry) under supervision of Prof. Ferenc Fülöp. During his doctoral studies, he exploited continuous flow catalytic processes for the sustainable synthesis of pharmaceutically relevant intermediates and potentially bioactive products. After completing Ph.D., he received a postdoctoral position at the Hungarian Academy of Sciences. In 2018, he moved to Austria and currently, he is a senior Post-Doc in the research group of Prof C. Oliver Kappe (CC FLOW) at University of Graz, Institute of Chemistry. His research interest is focused on the combination of flow chemistry, synthetic organic chemistry, organo- and transition metal catalysis, with a view to the synthesis and development of pharmacologically active compounds.

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Multigram-Scale Flow Synthesis of the Chiral Key Intermediate of (–)-Paroxetine Enabled by Solvent-Free Heterogeneous Organocatalysis

Friday, 15 November 2019 at 16:30

Add to Calendar ▼2019-11-15 16:30:002019-11-15 17:30:00Europe/LondonMultigram-Scale Flow Synthesis of the Chiral Key Intermediate of (–)-Paroxetine Enabled by Solvent-Free Heterogeneous OrganocatalysisFlow Chemistry Asia 2019 in Tokyo, JapanTokyo, JapanSELECTBIOenquiries@selectbiosciences.com

(–)-Paroxetine is a selective serotonin reuptake inhibitor which is broadly used for the treatment of depression, anxiety and panic disorder. It is currently manufactured by batch processes of 10?15 reaction steps which typically apply classical resolution methods, chiral auxiliaries, enzymatic asymmetrizations or naturally occurring homochiral starting materials as sources for asymmetry. Catalytic enantioselective transformations have also been harnessed for the synthesis of (–)-paroxetine. These methods require less synthetic steps and provide more direct access to the target API, but their applicability for manufacturing is limited by the low productivity of the catalytic asymmetric key step. Motivated by these limitations, we developed a flow process for the synthesis of the chiral phenylpiperidine key intermediate of (–)-paroxetine. The critical step to introduce asymmetry was a solvent-free enantioselective conjugate addition in the presence of a highly robust heterogeneous organocatalyst. The chiral adduct was processed further via a telescoped reductive amination?lactamization?amide/ester reduction sequence which took advantage of a heterogeneous catalytic hydrogenation approach and the application of neat BH3·dimethylsulfide complex as an efficient reducing agent unprecedented in earlier flow syntheses. The solvent-free or highly concentrated conditions in combination with the remarkably robust catalysts enabled multigram per hour scale production of the chiral target. In addition, the process generated minimal amounts of waste as demonstrated by a cumulative E-factor of 6.


Add to Calendar ▼2019-11-14 00:00:002019-11-15 00:00:00Europe/LondonFlow Chemistry Asia 2019Flow Chemistry Asia 2019 in Tokyo, JapanTokyo, JapanSELECTBIOenquiries@selectbiosciences.com