134664-69-0Relevant articles and documents
Tandem Wittig Reaction-Ring Contraction of Cyclobutanes: A Route to Functionalized Cyclopropanecarbaldehydes
Aitken, David J.,Caboni, Pierluigi,Cuccu, Federico,Frongia, Angelo,Luridiana, Alberto,Secci, Francesco,Serusi, Lorenzo
supporting information, (2019/10/08)
An original tandem reaction consisting of a Wittig reaction-ring contraction process between α-hydroxycyclobutanone and phosphonium ylides has been developed. Highly functionalized cyclopropanecarbaldehydes are obtained in good to high yield.
An Efficient and Cost-Effective Synthesis of Pagoclone
Stuk, Timothy L.,Assink, Bryce K.,Bates Jr., Ronald C.,Erdman, David T.,Fedij, Victor,Jennings, Sandra M.,Lassig, Jennifer A.,Smith, Randy J.,Smith, Traci L.
, p. 851 - 855 (2013/09/05)
The compound (+)-2-(7-chloro-1,8-naphthyridin-2-yl)-3S-(5-methyl-2- oxohexyl)-l-isoindolinone (pagoclone) shows anxiolytic activity due to partial agonism of the benzodiazepine site of the GABAA receptor. We describe the development of an economical and practical process for a 100+ kg pilot plant production used to supply development needs. For the key reaction, a β-keto phosphonium salt was prepared by selectively reacting a primary α-bromo ketone with triphenylphosphine in the presence of a secondary α-bromo ketone. A novel Wittig reaction with a 1-isoindolinone was used to produce racemic pagoclone. The enantiomerically pure drug substance was prepared by hydrolyzing a γ-lactam and resolving the resulting enantiomeric carboxylic acids with (+)-ephedrine hemihydrate. An alternate resolution, involving chiral multicolumn chromatography (MCC) was also developed. The synthesis was completed by a racemization-free lactam formation to afford pagoclone.
