Study Of The Synthetic Process Of Norethisterone

Norethisterone is a kind of female oral contraceptives developed in 1954. The product produced successfully in China in 1963 and subsequently in clinical trials as a contraceptive. Up to today, Norethisterone is still widely used in clinical practice as a short-acting oral contraceptives and visiting pills.The key of norethindrone is to obtain the key intermediate,4-androstene-19-nor-3,17-dione (19-norandrostenedione). The synthesis route reported in the literature use 5,16-pregnane diene-3p-ol-20-one-3-acetate (16-Dehydropregnenolone acetate) as starting material to obtain the key intermediate,4-androstene-19-nor-3,17-dione (19-norandrostenedione). The reaction steps include oximation, rearrangement, hydrolysis, addition, epoxy, hydrolysis, oxidation, elimination, reduction, ring opening, oxidation and elimination. Then 19-norandrostenedione can be reacted with acetylene gas to obtain norethisterone.The total yield is 23.5%. In the process, the benzene is used as solvent many times, and the toxic materials, chromium anhydride, is used also. And the steps are very cumbersome. We have improved to achieve a green synthesis, removes the solvent benzene, replaced Jones reagent by other oxidants, and improved reaction time, reaction temperature, increased yield in the new route. We have improved the ethynylation process, reduced reaction time, increased yield. The total yield was 28.3%.