Selected drug molecules including acetaminophen, allopurinol, and hydroxyzine were reacted with various silyl chlorides in the presence of base to form silyl ether derivatives for their potential use as prodrugs. Facile silylation of the drugs occurred using trimethylchlorosilane in the presence of triethylamine whereas chloride substitution of the bulkier monochlorosilanes, triisopropylchlorosilane and t-butyldimethylchlorosilane, generally required n-butyllithium for conversion to product. Reactions to prepare the disubstituted derivatives of acetaminophen and hydroxyzine and their mixed derivative using dimethyldichlorosilane will also be presented. Products were characterized by 1H, 13C and 29Si NMR spectroscopy. The bis(trimethylsilyl) derivative of allopurinol was characterized by X-ray crystallography.

Synthesis and characterization of silylated drug derivatives

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.