Kilogram-Scale Synthesis of 11β-Hydroxyandrosterone

This article describes a robust and large-scale synthesis of the ketosteroid building block 11β-hydroxyandrosterone (2) from cheap and readily available hydrocortisone (1). The initial discovery route, which was conducted on a gram scale and achieved a 3–6% yield over eight steps, is also described. Key to the route redesign was the incorporation of two stereoselective steps setting the desired 5α-H and 3α-OH chiral centers and optimization to minimize chromatographic purification. The process route was then conducted at the kilogram scale and achieved a 21–28% yield over four steps.