Preparation of trimethylsilyl derivatives of thiamphenicol

The silylation of thiamphenicol has been investigated. Treatment of thiamphenicol with hexamethyldisilazane or N-trimethylsilylimidazole, either alone or in the presence of trimethylchlorosilane, in acetonitrile or pyridine yields the bis(trimethylsily) (TMS) ether derivative. These procedures, however, cause to some extent the formation of 1-(p-methylsulphonylphenyl)-2-monochloroacetamido-1,3-propanediol. Silylation with N,O-bis(trimethylsilyl)acetamide gives, depending on the solvent used, the mono-, bis- and tris-TMS derivatives.