The reaction of 9beta,11beta-epoxy-17alpha,21-dihydroxy-16alpha-methyl-1,4-pregnadiene-3,20-dione (I) with MsCl in pyridine gives the corresponding 21-mesylate (II), which is treated with LiCl in the same solvent to yield 21-chloro-9beta,11beta-epoxy-17alpha-hydroxy-16alpha-methyl-1,4-pregnadiene-3,20-dione (III). The esterification of (III) with 2-furoyl chloride (IV) and TEA affords the expected ester (IV), which is finally treated with anhydrous HCl in acetic acid in order to open the epoxide ring to provide the target mometasone furoate. A similar reaction sequence can be performed using p-toluenesulfonyl chloride instead of mesyl chloride in the first step of the sequence.
The esterification of 21-chloro-17alpha-hydroxy-16alpha-methyl-1,4,9(11)-pregnatriene-3,20-dione (I) with 2-furoyl chloride (II) by means of TEA gives the corresponding ester (III), which is then treated with HClO4 and 1,3-dichloro-5,5-dimethylhydantoin (DDH) in THF/water in order to add Cl-OH to the 9(11)-double bond of ester (III).
By esterification of mometasone (I) with 2-furoyl chloride (II) by means of TEA in dichloromethane.