Original Article:
Redesign of a Grignard-Based Active Pharmaceutical Ingredient (API) Batch Synthesis to a Flow Process for the Preparation of Melitracen HCl
Michael J. Pedersen, et al.
Org. Process Res. Dev. 2018, 22(2), 228-235.
10.1021/acs.oprd.7b00368
The active pharmaceutical ingredient (API) Melitracen (HCl) has been used to treat depression and anxiety. The Grignard reaction is a common method for carbon-carbon bond formation in API development. As illustrated in the figure, four synthetic steps are involved in the manufacturing of Melitracen HCl. The four steps are a classic Grignard addition to a ketone, a hydrolysis of a magnesium alkoxide, a dehydration of an alcohol and a salt precipitation to isolate the API. The Grignard addition is between 10,10-dimethylanthrone (10,10-DMA) and 3-(N,N-dimethylamino)propylmagnesium chloride (DMPC-MgCl), 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. This work focuses on the redesign of the Grignard-based batch process for the preparation of Melitracen HCl to fit a continuous reactor system. The results show that the process setup benefits from a reduced footprint, lower energy consumption, fewer synthesis steps, and less raw material usage compared to batch processes.
Chemicals Related in the Paper:
| Catalog Number | Product Name | Structure | CAS Number | Price |
|---|---|---|---|---|
| ACM10563709 | Melitracen hydrochloride |  |
10563-70-9 | Price |
