Practical and scalable synthesis of beclomethasone dipropionate

Beclomethasone dipropionate (1) is a synthetic corticosteroid with anti-inflammatory, antipruritic, and anti allergy properties. It is widely used to treat asthma, allergic rhinitis, and dermatoses. However, existing synthetic routes to this active pharmaceutical ingredient (API) contain steps resulting in low and/or inconsistent yields, and use obsolete reagents. Such inconsistencies coupled with a lack of reliable experimental data makes laboratory-scale and large-scale synthesis of this API difficult and time-consuming. In this paper, we report a practical and scalable approach to synthesize 1 from the readily available steroidal intermediate, 16 beta-methyl epoxide (3, DB-11). A gram-scale to kilogram-scale synthesis of 1 was achieved with 82% yield, using a costeffective and scalable methodology. Selective propionylation of the hydroxyl groups at C-17 and C-21 demonstrate the fact that this approach can be conveniently implemented in fine chemical industries.

Automated summary

Beclomethasone dipropionate is a synthetic corticosteroid with anti-inflammatory, antipruritic, and anti-allergy properties. Current synthetic routes to this active pharmaceutical ingredient suffer from low and inconsistent yields, as well as the use of outdated reagents. This paper presents a practical and scalable approach to synthesize Beclomethasone dipropionate using a readily available steroidal intermediate.