Grignard Reagent-Based Flow Process for the Preparation of Melitracen Hydrochloride
Pedersen M J, et al. Organic Process Research & Development, 2018, 22(2), 228-235.
The manufacture of melitracen hydrochloride involves four synthetic steps. The four steps are the classic Grignard addition of ketones, hydrolysis of the magnesium alkoxide, dehydration of the alcohol, and salt precipitation to isolate the API. The Grignard addition is between 10,10-dimethylanthrone (10,10-DMA (1)) and 3-(N,N-dimethylamino)propylmagnesium chloride (DMPC-MgCl (2)), resulting in formation of the magnesium alkoxide 3. The magnesium alkoxide 3 is then hydrolyzed to the alcohol 4 and dehydrated to form product 5. The last step is a crystallization of the API as a salt, where HCl is added to obtain the Melitracen HCl (6).
· This work described the laboratory work for redesigning the process to fit a continuous reactor setup for the Grignard addition to the final Melitracen HCl crystallization. A flow diagram of a redesigned flow reactor setup for the synthesis of melitracen HCl is shown on the right.
· The flow process was significantly simplified compared to the batch process, with removal of a phase separation and usage of tetrahydrofuran (THF) only as a solvent compared to the previous toluene-THF solvent mixture. All synthetic steps were carried out at ambient temperature, whereas routine batch production requires active heating (up to 50°C) and cooling in several steps.
Solid Contact ISE Analysis Method of Melitracen Hydrochloride
Abdallah N A.Journal of The Electrochemical Society, 2020, 167(4), 047504.
Melitracen hydrochloride (MEL) is a tricyclic antidepressant. It works by inhibiting neuronal uptake of norepinephrine and serotonin. Commonly used methods for the determination of melitracen hydrochloride include spectrophotometry, densitometry, HPLC-UV, GC-MS, and LC-MS. This work developed a new potentiometric sensor for analyzing MEL based on electrochemical methods. The sensor was suitable for selective determination of MEL in bulk, pharmaceutical products and human plasma, as well as for studying dissolution profiles of pharmaceutical tablets.
· TiO2 nanoparticles were chosen to decorate the MWCNTs surface, which was further vinyl-functionalized to allow the copolymerization with functional monomers and cross-linkers in the presence of the template molecules to form the molecularly imprinted polymers (MIPs).
· Modified carbon paste electrodes (CPE) are made by uniformly mixing grafted multi-walled carbon nanotubes and graphite powder in the presence of a binder.
· The binding capacity of the prepared MWCNTs-TiO2-MIP nano-composite was examined by suspending 10 mg of the nano-composite into 5 ml of different initial concentrations of MEL standard solutions. The mixtures were kept under continuous shaking for 6 h at room temperature for the adsorption of MEL.
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