Process Research On Key Intermediates In The Manufacturing Of Deflazacort

Based on the literature survey, we designed and optimized the synthetic process of the third glucocorticoid deflazacort, as well as the preparation of its key intermediates.First we designed the following synthetic routes: by using 4,9(11),16-Pregnatetraene-3,20-dione as raw material, 20 carbonyl groupwas protected by methyl hydrazinocarboxylate, and the ?-epoxy ring was selectivelyopened directlywith ammonia. ?,?-amino alcoholreacted with acetic anhydride to form oxazoline ring, which was treated with pyruvic acid to remove the hydrazone protection group and obtained the key intermediate of deflazacort. After that, 21-position of this intermediate was introduced an actoxyl group by iodization and ester exchange. Finally, by bromohydroxylation and reduction debromination by tri-n-butyltin hydride/AIBN obtained deflazacort, total 9 steps reaction was applied in this process.. This process such advantages, such as easily operation, lower cost, higher yield and less time consume compared with original process, all of them displayed potential good industrial application value.The major issues on reaction conditions of key steps were furtheroptimized, and the total yieldwas improved to 20.3% and the HPLC purity of deflazacort was greater than99.7%. The structure of deflazacortwas confirmed by 1HNMR,melting point and comparing with the authority sample of deflazacort by HPLC method.