14035-96-2Relevant articles and documents
A Biocatalytic Route to the Novel Antiepileptic Drug Brivaracetam
Schülé, Arnaud,Merschaert, Alain,Szczepaniak, Christophe,Maréchal, Christophe,Carly, Nicolas,O'Rourke, John,Ates, Célal
, p. 1566 - 1575 (2016)
An asymmetric synthesis of the novel antiepileptic drug Brivaracetam 1 is described. The stereochemistry of the 4-n-propyl substituent is introduced by a biocatalytic resolution of (rac)-methyl 2-propylsuccinate 4-tert-butyl ester 4. The selection of the resolution substrate and the screening of enzymes were carried out from our in-house screening platform. The development and scale-up of the best conditions, including solvent media, pH control, workup, and enzyme supply, led up to a successful demonstration conducted at 1 kg scale in a 10 L vessel. The chiral intermediate (R)-2-propylsuccinic acid 4-tert-butyl ester 6 was reproducibly obtained in 42% yield and 97% ee all along the development. The control of the stereochemistry via the biocatalytic resolution allowed the production of Brivaracetam 1 within the required commercial quality specifications.
Ketenimines from Isocyanides and Allyl Carbonates: Palladium-Catalyzed Synthesis of β,γ-Unsaturated Amides and Tetrazoles
Qiu, Guanyinsheng,Mamboury, Mathias,Wang, Qian,Zhu, Jieping
supporting information, p. 15377 - 15381 (2016/12/06)
The reaction of allyl ethyl carbonates with isocyanides in the presence of a catalytic amount of Pd(OAc)2provided ketenimines through β-hydride elimination of the allyl imidoylpalladium intermediates. The insertion of the isocyanide into the π-allyl Pd complex proceeded via an unusual η1-allyl Pd species. The resulting ketenimines were hydrolyzed to β,γ-unsaturated carboxamides during purification by flash column chromatography on silica gel or converted in situ into 1,5-disubstituted tetrazoles by [3+2] cycloaddition with hydrazoic acid or trimethylsilyl azide.
Unprecedented hydrogen transfer from water to alkenes and alkynes mediated by TiIII and late transition metals
Campana, Araceli G.,Estevez, Rosa E.,Fuentes, Noelia,Rubles, Rafael,Cuerva, Juan M.,Bunuel, Elena,Cardenas, Diego,Oltra, J. Enrique
, p. 2195 - 2198 (2008/02/04)
We describe how alkenes and alkynes can be hydrogenated under mild conditions by hydrogen transfer from water mediated by titanocene(III) and a substoichiometric quantity of one of the late transition metals usually employed as hydrogenation catalysts. This process proceeds presumably by H-atom transfer from TiIII-coordinated water to the late transition metal partner (depicted in the drawing above), a mechanism in support of which we provide theoretical and experimental evidence.
