The dehydrogenation of 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4-diene-3,20-dione-21-acetate (I) with dichlorodicyanobenzoquinone (II) in dioxane HCl gives 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-21-acetate (III), which is hydrolyzed with aqueous NaHCO3 to the corresponding free triol (IV). The reaction of (IV) with triethyl orthopropionate (A) by means of p-toluenesulfonic acid in DMSO yields 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17,21-ethylorthopropionate (V), which is hydrolyzed partially with acetic acid to 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17-propionate (VI). The acylation of (VI) with propionic anhydride affords 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17,21-dipropionate (VII), which is finally treated with dry HCl in dioxane.

The dehydrogenation of 16alpha-methyl-17alpha,21-dihydroxypregna-1,4-diene-3,11,20-trione-21-acetate (VIII) with (II) in dioxane-HCl gives 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-21-acetate (IX), which is hydrolyzed with aqueous NaHCO3 to the corresponding free diol (X). The reaction of (X) with triethyl orthopropionate (A) as before yields 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-17,21-ethylorthopropionate (XI), which is hydrolyzed partially with acetic acid to 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-17-propionate (XII). The acylation of (XII) with propionic anhydride yields the corresponding dipropionate (XIII), which is treated with dry HCl in dioxane to afford 16alpha-methyl-17alpha,21-dihydroxy-7alpha-chloropregna-1,4-diene-3,11,20-trione 17,21-dipropionate (XIV). Finally, this compound is reduced with NaSH4 in methanol - THF.

The dehydrogenation of 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4-diene-3,20-dione-21-acetate (I) with dichlorodicyanobenzoquinone (II) in dioxane HCl gives 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-21-acetate (III), which is hydrolyzed with aqueous NaHCO3 to the corresponding free triol (IV). The reaction of (IV) with triethyl orthopropionate (A) by means of p-toluenesulfonic acid in DMSO yields 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17,21-ethylorthopropionate (V), which is hydrolyzed partially with acetic acid to 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17-propionate (VI). The acylation of (VI) with propionic anhydride affords 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17,21-dipropionate (VII), which is finally treated with dry HCl in dioxane.

The dehydrogenation of 16alpha-methyl-17alpha,21-dihydroxypregna-1,4-diene-3,11,20-trione-21-acetate (VIII) with (II) in dioxane-HCl gives 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-21-acetate (IX), which is hydrolyzed with aqueous NaHCO3 to the corresponding free diol (X). The reaction of (X) with triethyl orthopropionate (A) as before yields 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-17,21-ethylorthopropionate (XI), which is hydrolyzed partially with acetic acid to 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-17-propionate (XII). The acylation of (XII) with propionic anhydride yields the corresponding dipropionate (XIII), which is treated with dry HCl in dioxane to afford 16alpha-methyl-17alpha,21-dihydroxy-7alpha-chloropregna-1,4-diene-3,11,20-trione 17,21-dipropionate (XIV). Finally, this compound is reduced with NaSH4 in methanol - THF.

The dehydrogenation of 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4-diene-3,20-dione-21-acetate (I) with dichlorodicyanobenzoquinone (II) in dioxane HCl gives 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-21-acetate (III), which is hydrolyzed with aqueous NaHCO3 to the corresponding free triol (IV). The reaction of (IV) with triethyl orthopropionate (A) by means of p-toluenesulfonic acid in DMSO yields 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17,21-ethylorthopropionate (V), which is hydrolyzed partially with acetic acid to 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17-propionate (VI). The acylation of (VI) with propionic anhydride affords 16alpha-methyl-11beta,17alpha,21-trihydroxypregna-1,4,6-triene-3,20-dione-17,21-dipropionate (VII), which is finally treated with dry HCl in dioxane.

The dehydrogenation of 16alpha-methyl-17alpha,21-dihydroxypregna-1,4-diene-3,11,20-trione-21-acetate (VIII) with (II) in dioxane-HCl gives 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-21-acetate (IX), which is hydrolyzed with aqueous NaHCO3 to the corresponding free diol (X). The reaction of (X) with triethyl orthopropionate (A) as before yields 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-17,21-ethylorthopropionate (XI), which is hydrolyzed partially with acetic acid to 16alpha-methyl-17alpha,21-dihydroxypregna-1,4,6-triene-3,11,20-trione-17-propionate (XII). The acylation of (XII) with propionic anhydride yields the corresponding dipropionate (XIII), which is treated with dry HCl in dioxane to afford 16alpha-methyl-17alpha,21-dihydroxy-7alpha-chloropregna-1,4-diene-3,11,20-trione 17,21-dipropionate (XIV). Finally, this compound is reduced with NaSH4 in methanol - THF.

In a different method, the primary amine (XVIII) was prepared by reduction of nitrile (XI) with either borane-dimethyl sulfide complex or with LiAlH4. Condensation of amine (XVIII) with acetophenone (I) generated imine (XIX). The asymmetric reduction of (XIX) to furnish the title (R)-amine was accomplished by using LiAlH4 in the presence of several chiral auxiliaries, such as 1,1?binaphthol, (-)-N-methylephedrine, or (-)-N-methylpseudoephedrine, with different degrees of enantioselectivity. Alternatively, imine (XIX) was reduced utilizing a titanium-catalyzed asymmetric hydrosilylation method.