Acceleration of Anti‐Markovnikov Hydroamination in the Synthesis of an Active Pharmaceutical Ingredient |
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| Authors: | Aleksandar Mitic Tommy Skovby Kim Dam‐Johansen Krist V Gernaey |
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| Affiliation: | 1. CAPEC‐PROCESS Research Center, Department of Chemical and Biochemical Engineering, Technical University of Denmark (DTU), Kgs. Lyngby, Denmark.;2. H. Lundbeck A/S, Chemical Production Development, Nykoebing Sj., Denmark.;3. CHEC Research Center, Department of Chemical and Biochemical Engineering, Technical University of Denmark (DTU), Kgs. Lyngby, Denmark. |
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| Abstract: | Slow chemical reactions are a big challenge in the modern pharmaceutical industry. Their accelerations together with the introduction of continuous manufacturing modes are major drivers for future development. One example reaction is hydroamination, a reaction between unsaturated hydrocarbons and amines. Such a reaction type is the main focus of this work. More precisely, the anti‐Markovnikov hydroamination reaction between cis/trans 9H‐thioxanthene‐2‐chloro‐9‐(2‐propenylidene)‐(9CI) and 1‐(2‐hydroxyethyl)piperazine (HEP) is investigated in detail. It has been traditionally performed in toluene with a huge excess of HEP and reaction times of up to 24 h. Acceleration of the reaction from 24 down to 4 h is achieved by switching from batch operation mode in toluene to either solvent‐free batch mode or microwave‐assisted hydroamination with tetrahydrofuran as a solvent. |
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| Keywords: | Active pharmaceutical ingredient Hydroamination reaction Microwave‐assisted organic synthesis Solvent‐free synthesis |
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