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.

• Technical University of Denmark (DTU)
• H Lundbeck & Co AS
• Technical University of Denmark

• API

1. Active pharmaceutical ingredient
2. API
3. Hydroamination reaction
4. Microwave-assisted organic synthesis
5. Research Article
6. Solvent-free synthesis