An Efficient Method for the Synthesis of Adapalene as an Active Pharmaceutical Ingredient Using Zinc Nanoparticles

Document Type : Research Article

Authors

Department of Chemistry, Amirkabir University of Technology, P.O. Box 13145-659 Tehran, I.R. IRAN

Abstract

In this study, the synthesis of adapalene as an active pharmaceutical ingredient on a laboratory scale is examined. Our effort was focused on catalyzing C-C coupling as a difficult step in the adapalene total synthesis, using the zinc nanoparticles as well as eliminating the magnesium reagent. The use of zinc nanoparticles in C-C coupling is associated with increased yields compared with its bulk powder form. The best results were obtained using 1- (5-bromo-2-methoxy phenyl) adamantane and methyl 6-bromo-2-naphthoate in the presence of zinc nanoparticles in dry tetrahydrofuran followed by adding NiCl2 (DPPE) as the catalyst. Replacing the magnesium with zinc nanoparticles, this reaction can scale up to higher scales.

Keywords

Main Subjects

References

[1] Roucoux A., Schulz J., Patin H., Reduced Transition Metal Colloids: A Novel Family of Reusable Catalysts?, Chem. Rev., 102(10): 3757–3778 (2002).
[2] Gawish S.M., Avci H., Ramadan A.M., Mosleh S., Monticello R., Breidt F., Kotek R., Properties of Antibacterial Polypropylene/Nanometal Composite Fibers, J. Biomater. Sci.,Polym., 23(1): 43–61 (2012).
[3] Chandra S., Kumar A., Modulation of Synthetic Parameters of Novel Zinc Nanoparticles and Reducing Agent: Powder X-Ray Diffraction, Transmission Electron Microscopy and Spectral Studies, Spectrochim. Acta, Part A, 97: 935–941 (2012).
[4] Shroot B., Eustache J., Bernardon J.M., Benzonaphthalene Derivatives and Compositions, U.S. Patent 4,717,720 (1988).
[5] Serrano J.P., Medichem S.A., Process for the Preparation of Adapalene and Related Compounds, U.S.Patent.8,119,834 (2012).
[6] Vyas K.D., Nair R., Nalawade P., Patil U.D., Panandikar A.M., Novel Process for Preparation of Adapalene, W.O. Patent 126,104 (2008).
[7] Castaldi G., Allegrini P., Razzetti G., Ercoli M., Process for the Preparation of Adapalene, U.S. Patent 7,345,189 (2008).
[8] Pilgrim W.R., Lagiere J., Process for the Preparation of 1-Adamantane Derivatives, U.S. Patent 5,015,758 (1991).
[9] Liu Z., Xiang J., A High yield and Pilot-Scale Process for the Preparation of Adapalene, Org. Process Res. Dev., 10(2): 285–288 (2006).
[10] Kalvinsh I., Chernobrovijs A., Tribulovich V., Labeish V., Process for Preparation of 6-[3-(1-admantyl)-4-methoxyphenyl]-2-naphtoic acid, U.S. Patent Application 12/448,670 (2007).
[11] Ghanta S.R., Rao M.H., Muralidharan K., Single-Pot Synthesis of Zinc Nanoparticles, Borane (BH3) and Closo-Dodecaborate (B12H12)2− Using LiBH4 under mild Conditions, Dalton Trans., 42(23): 8420–8425 (2013).

Files

Share

How to cite

Statistics