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Process Research on the Preparation of 1-(3-Trimethylsilylphenyl)-2,2,2-trifluoroethanone by a Friedel–Crafts acylation Reaction

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journal contribution
posted on 18.01.2008, 00:00 by Richard A. Wolf
Zifrosilone (1-(3-trimethylsilylphenyl)-2,2,2-trifluoroethanone) (3) is a cholinesterase inhibitor that has been studied for the treatment of Alzheimer’s disease. Process research has been carried out on a route to convert phenyltrimethylsilane to 3 by Friedel–Crafts acylation using trifluoroacetic anhydride. Kinetics and products analyses suggest that the optimal conditions for this reaction are noncatalytic amounts of aluminum chloride, dichloromethane solvent and as low a temperature as can be practically used in a scaled-up process. Significant separation challenges to isolate 3 from the isomer byproduct 1-(4-trimethylsilylphenyl)-2,2,2-trifluoroethanone) (4) remain. These challenges were investigated using vapor–liquid equilibrium studies.