1253291-12-1Relevant articles and documents
Difluoromethylation of Phenols and Thiophenols with the S-(Difluo-romethyl)sulfonium Salt: Reaction, Scope, and Mechanistic Study
Liu, Guo-Kai,Qin, Wen-Bing,Li, Xin,Lin, Li-Ting,Wong, Henry N. C.
, p. 15948 - 15957 (2019/11/16)
A facile and practical approach for the difluoromethylation of phenols and thiophenols was described. Making use of the recently developed bench-stable S-(difluoromethyl)sulfonium salt as the difluorocarbene precursor, a wide variety of diversely functionalized phenols and thiophenols were readily converted to their corresponding aryl difluoromethyl ethers in good to excellent yields in the presence of lithium hydroxide. Chemoselectivity of various O,S-nucleophiles toward difluorocarbene was systematically studied, suggesting the reactivity order ArS- > RS-, ArO- > ROH > RO-, ArSH, ArOH, RSH.
A robust process for an mGluR5 negative allosteric modulator: Difluoromethylation and sonogashira coupling on large scale
Sperry, Jeffrey B.,Farr, Roger M.,Levent, Mahmut,Ghosh, Mousumi,Hoagland, Steven M.,Varsolona, Richard J.,Sutherland, Karen
, p. 1854 - 1860 (2013/01/15)
The development of the potent and selective mGluR5 negative allosteric modulator (NAM) 1 is described. Key features in the process, which has been implemented on a multikilogram scale, include a high-temperature difluoromethylation reaction, a Sonogashira coupling, and careful control of residual Pd and Cu in the final API. Due to the relative nonpolar nature of the intermediates, water-miscible solvents were employed in all four steps to allow for direct crystallizations upon reaction completion. In addition, several crystalline morphologies of the API were discovered, and the isolation of the desired form II will be discussed.
