4’-tert-Butyldimethylsilyl-6-hydroxy Raloxifene

The preparation of the Raloxifene 6-glucuronide includes: (a) reaction of Raloxifene with tertbutyldimethylsilyl chloride to give a chromatographically separable mixture of Compound 3 and 4'-tert-Butyldimethylsilyl-6-hydroxy Raloxifene (Compound 4); (b) Lewis acid mediated coupling of phenol 4'-tert-Butyldimethylsilyl-6-hydroxy Raloxifene with methyl1,2,3,4-tetra-O-acetyl-D-glucopyranuronate to provide a single product (Compound 6) with the desired flstereochemistry at the anomeric center; (c) heating Compound 6 with lithium hydroxide in dioxane to 60°C, followed by deprotection with tetrabutylammonium fluoride to give Raloxifene 6-glucuronide.