The Oxidation of a Sterically Hindered Axial Secondary Alcohol with the Catalyst 4-Hydroxy-TEMPO under Acidic Conditions

Abstract

At companies such as Pfizer, pharmaceutical processes are constantly being changed or optimized for a variety of different reasons. These reasons include environmental factors, efficiency of process and production, or making the process more affordable for the plant and consequently the patient. This project began with the development of a more efficient process to make a potential starting material for an active pharmaceutical ingredient (API) manufactured in Kalamazoo. The new starting material is identical to the one currently used with the exception of the stereochemistry of a key secondary alcohol that is oxidized in the next chemical transformation. The new starting material features the hydroxyl group in an axial position instead of the equatorial. Whether the difference in stereochemistry affects the reactivity when it comes to oxidation was the focus of this project. Six different oxidation reactions were screened on the two starting materials. The results showed that the orientation (axial vs. equatorial) affected whether a given condition was capable of oxidizing the hydroxyl group. Based on the initial screen, the most successful oxidation conditions for the new starting material were selected for optimization. A design of experiments (DOE) was conducted on the reaction to find optimal conditions, which were scaled-up in the laboratory. Further investigation into quench, workup and isolation along with other factors are necessary for future development of this process.