Studies On The Synthetic Processes For The Dehalogenation To Produce The Corresponding 11β-hydroxy Steroids

The importing of 11β-hydroxy into steroid occupies the extremely important position in the chemistry of steroid pharmaceuticals. The process for dehalogenation of a 9α-halosteroids is a prevalent way of chemosynthesis in industrialized process, but some kittle questions still exist. The first one is that the yields are extremely low and there is a large elevated space. The second is that the ratio of the corresponding undesired ?9(11) steroid to the 11β-hydroxy steroid is high. The ratio of ?9(11) is general 4-5% in the existing produce level. And the ratio is very important due to the difficulty of removing the ?9(11) compound from the 11β-hydroxy product.Therefore, the synthetic process is studied in the thesis based on radical mechanisms of the process for dehalogenation of 9α-halosteroids and starting with 9α-bromo-11β,17α-dihydroxypregna-6α-methylpregna-4-ene-3,20-dione-21-acetate. (1) Adding zinc powder into the reactive system and replacing unstable chromium (+2) with chromium (+3) , to recycle chromium(+2) and reduce amounts of chromium(+2) in the reactive system; (2) Changing the order and manner of adding the reactants to obtain more desired product; (3) Ascertaining six experimental factors by orthogonal experimental analysis method and design of 18 experiments and 5 complementary experimental projects to optimize reactive parameters; (4) Discovering the main influencing factors to the experimental aims by the orthogonal experiments; (5) Putting up the stability experiments with the founded optimal reactive parameters.By the study of the synthetic process the optimal synthetic process of the dehalogenation reaction is founded starting with 9α-bromo-11β,17α-dihydroxypregna -6α-methylpregna-4-ene-3,20-dione-21-acetate. The yield is more than 75.0%. The purity of the desired product determined by HPLC is more than 95.0% and the radio of the undesired product (11β,17α-dihydroxypregna-6α-methylpregna-4,9-diene-3,20- dione-21-acetate) is less than 2.5%. Basically the prospective goal came true.