Selective synthesis of 4-methoxyestrogen from 4-hydroxyestrogen

The introduction of an oxygen atom into the C-6 position of 4-hydroxyestrog en allowed for the selective methylation of the two phenolic hydroxyl group s. When the B-oxo derivative of 4-hydroxyestrone was benzylated in ethanol, only the 3-monobenzyl ether was obtained without formation of the 4-monobe nzyl ether. Moreover, the 6-carbonyl group was further reduced to methylene almost quantitatively in the reaction of 4-acetoxy-6-oxoestrone 3-benzyl e ther derivative with sodium borohydride. Therefore, 4-methoxyestrogen was s ynthesized by essentially combining these two reactions. (C) 2001 Elsevier Science Inc. All rights reserved.