Preparation of Two Process-Related Impurities of a Key Intermediate of Silodosin Under Baeyer–Villiger and Fenton Conditions

Control of process-related impurities is of critical importance for developing an efficient and suitable synthetic process of an active pharmaceutical ingredient. In the study of a key intermediate of silodosin (KIS), two process-related impurities including the benzaldehyde impurity (BAI) and indole impurity (IDI) were prepared and fully characterized to determine their downstream fate. Under optimized conditions, BAI was formed in a yield of ~48% by treating KIS with 10% hydrogen peroxide at 60 °C. Interestingly, BAI would not be expected to be the major product under the apparent Baeyer–Villiger oxidative condition. Furthermore, by adding 20 mM FeCl3 into the above 10% hydrogen peroxide solution, IDI became the major product in a yield of ~43% under this Fenton reaction-like condition. The probable formation mechanism of IDI was discussed and validated in the context of certain structurally similar substrates.