| 摘要 |
A fluorination method for preparing 21-fluoro-pregnanes and also methods of preparing 9 alpha ,11 beta -dichloro-6 alpha ,21-difluoro-16 alpha ,17 alpha -alkylidenedioxy-pregna-1,4-diene-3,20-dione and 9 alpha ,11 beta -dichloro-6 alpha ,21-difluoro-16 alpha ,17 alpha -alkylidenedioxy-pregn-4-ene-3,20-dione derivatives from the corresponding 21-acyloxy-6 alpha -fluoro-16 alpha ,17 alpha -alkylidenedioxy-3,20-diketo-pregnane derivatives. The fluorination process comprises (1) displacement of the corresponding 21-mesyloxy, or 21-tosyloxy, pregnane derivative with bromide ion to yield the corresponding 21-bromo pregnane derivative, and (2) displacement with fluoride ion to effect replacement of the 21-bromo thereby yielding the corresponding 21-fluoro pregnane derivative. A salient feature is the use of a sulfone solvent in the fluoride displacement step, thereby affording improved yields and purer products. The process of preparing 9 alpha ,11 beta -dichloro-6 alpha ,21-difluoro-16 alpha ,17 alpha -alkylidenedioxy-3,20-keto-pregna-1,4-diene or -pregn-4-ene derivatives comprises treating the corresponding 21-bromo-6 alpha -fluoro-16 alpha ,17 alpha -alkylidenedioxy-3,20-dione-pregnane derivatives according to the aforementioned displacement process in combination with a subsequent 9 alpha ,11 beta -chlorination process. The aforementioned processes are characterized by high yields and high purity products.
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