Hydrocortisone can also be synthesized from cortisone acetate. It is treated with semi-carbazide, during which the disemicarbazone 27.1.18 is formed as a result of a reaction at both carbonyl groups at C3 and C20. The carbonyl group at C11 is reduced by potassium borohydride to an alcohol group, during which the acetyl group on the hydroxyl at C21 is simultaneously removed, giving semicarbazone 27.1.19. By removing the semicarbazide protection using nitric acid, hydrocortisone (27.1.8) is formed.

Hydrocortisone is used in the form of a free alcohol (speaking of the hydroxyl group at C21), as well as in the form of an acetate, succinate, or phosphate [8].

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