Fluocinolone acetonide (I) was selectively mesylated at the primary alcohol group by means of methanesulfonyl chloride and pyridine. Treatment of the resulting mesylate (II) with alpha-mercapto-gamma-butyrolactone (IV) in the presence of NaH in THF produced the desired thioether derivative.
Ketal exchange of acetonide (I) with butyraldehyde (II) under acidic conditions provides the corresponding butylidene ketal (III). The primary alcohol group of (III) is then mesylated with methanesulfonyl chloride in pyridine to furnish (IV). Subsequent displacement of the mesylate group of (IV) by racemic alpha-mercapto-gamma-butyrolactone (V) gives rise to a mixture of the title compound along with its (R)-epimer (VI), which can be separated employing preparative HPLC. (1,2)