Dydrogesterone (DG) is a potent progesterone drug that can be used to treat almost all progesterone-deficiency in women. However, there are few reports on DG process studies, and the by-products are unclear, which make the process optimization challenging. In this paper, we report the process optimization studies for the synthesis of 9α,10β-pregest-5,7-diene-3,20-diethylene glycol ketone (1), an intermediate of DG. Starting from the natural raw progesterone, the intermediate 1 was synthesised