Silver-Mediated Trifluoromethoxylation of Aryl Nucleophiles and Synthesis of 3-Deoxy-3-Fluoromorphine
Contributors: Ritter, Tobias; Jacobsen, Eric N.; Betley, Theodore A.
Published: 2012
Language: eng
Description: Fluorine incorporation has become increasingly important in pharmaceutical applications. Upon fluorination and incorporation of fluorinated moieties such as trifluoromethoxy groups, many small molecules become more bioavailable and metabolically stable and additionally can better cross the blood-brain-barrier. This thesis describes the development of a method mediated by silver salts for the synthesis of pharmaceutical-like trifluoromethoxylated compounds via C&ndash;OCF3 bond formation. Additionally, the synthesis of 3-deoxy-3-fluoromorphine via late-stage fluorination of morphine is described as well as in vitro and in vivo evaluation of 3-deoxy-3-fluoromorphine as a potential analgesic.
Notes: Keywords: antinociception, aryl trifluoromethyl ethers, cross-coupling, fluorinated morphine, silver-mediated, trifluoromethoxylation.

Thesis Ph.D. Harvard University 2012