Synthesis of 3α-hydroxy-21-(1′-imidazolyl)-3β-methoxyl-methyl-5α-pregnan-20-one via lithium imidazole with 17α-acetylbromopregnanone

The synthesis of biologically active 3α-hydroxyl-21-(1′-imidazolyl)-3β-methoxymethyl-5α-pregnan-20-one (11) was accomplished in six steps. The key steps were the improvement of stereoselectivity for acetyl isomers in C-17 and the introduction of imidazole into the core structure by use of lithium imidazole. This latter key step provided the desired product 11 in 82% yield without the formation of 1,3-disubstituted imidazolium salt as impurity, which is generally observed in traditional method.

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