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.

中文翻译：

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Friedel-Crafts酰化反应制备1-（3-三甲基甲硅烷基苯基）-2,2,2-三氟乙酮的工艺研究

Zifrosilone（1-（3-trimethylsilylphenyl）-2,2,2-trifluoroethanone）（3）是胆碱酯酶抑制剂，已被研究用于治疗阿尔茨海默氏病。已经进行了工艺研究，该工艺使用三氟乙酸酐通过Friedel-Crafts酰化将苯基三甲基硅烷转化为3。动力学和产物分析表明，该反应的最佳条件是非催化量的氯化铝，二氯甲烷溶剂，以及如在放大工艺中实际使用的温度一样低的温度。从异构体副产物1-（4-三甲基甲硅烷基苯基）-2,2,2-三氟乙酮中分离3的重大分离挑战（4） 保持。使用汽液平衡研究对这些挑战进行了研究。