54256-51-8Relevant articles and documents
Synthesis of Fingolimod Employing Regioselective Aziridine Ring-Opening Reaction as a Key Step
Cinibulk, Josef,Doubsky, Jan,Klvaňa, Robert,Rádl, Stanislav
, (2021/09/18)
An efficient and scalable synthesis of the immunomodulating drug fingolimod hydrochloride has been developed with the aziridine regioselective ring-opening reaction as a key step. This manuscript describes design, detailed synthetic route scouting, and optimization study of the aziridine ring-opening reaction. As a starting material for the polar part of the fingolimod molecule, cheap, common, and widely commercially available tris(hydroxymethyl)aminomethane was used. n-Octyl group was introduced into the molecule either via Kumada or Negishi cross-couplings, or alternatively by Sonogashira cross-coupling followed by hydrogenation. The final step consists of a one-pot acidic deprotection both of the acetonide and Boc group, providing thus highly pure fingolimod hydrochloride from the crude reaction mixture directly. The described process is highly effective, is industrially applicable, and has been successfully applied to 500 g scales of the target product.
Radical Chain Reduction via Carbon Dioxide Radical Anion (CO2?-)
Hendy, Cecilia M.,Smith, Gavin C.,Xu, Zihao,Lian, Tianquan,Jui, Nathan T.
supporting information, p. 8987 - 8992 (2021/07/01)
We developed an effective method for reductive radical formation that utilizes the radical anion of carbon dioxide (CO2?-) as a powerful single electron reductant. Through a polarity matched hydrogen atom transfer (HAT) between an electrophilic radical and a formate salt, CO2?- formation occurs as a key element in a new radical chain reaction. Here, radical chain initiation can be performed through photochemical or thermal means, and we illustrate the ability of this approach to accomplish reductive activation of a range of substrate classes. Specifically, we employed this strategy in the intermolecular hydroarylation of unactivated alkenes with (hetero)aryl chlorides/bromides, radical deamination of arylammonium salts, aliphatic ketyl radical formation, and sulfonamide cleavage. We show that the reactivity of CO2?- with electron-poor olefins results in either single electron reduction or alkene hydrocarboxylation, where substrate reduction potentials can be utilized to predict reaction outcome.
Nickel-Catalyzed Cross-Electrophile Coupling of Aryl Chlorides with Primary Alkyl Chlorides
Gilbert, Michael M.,Goldfogel, Matthew J.,Kim, Seoyoung,Weix, Daniel J.
supporting information, p. 9902 - 9907 (2020/06/27)
Alkyl chlorides and aryl chlorides are among the most abundant and stable carbon electrophiles. Although their coupling with carbon nucleophiles is well developed, the cross-electrophile coupling of aryl chlorides with alkyl chlorides has remained a chall
