Data di Pubblicazione:
2017
Citazione:
In-flow synthesis of advanced precursors of Chiral APIs / M. Pirola, D. Brenna, L.M. Raimondi, A.J. Burke, M. Benaglia. ((Intervento presentato al convegno Corbella Summer School tenutosi a Gargnano nel 2017.
Abstract:
In the field of APIs (Active Pharmaceutical Ingredients), the industry is gradually progressing towards enantiopure formulations. In this context, chiral amines are unanimously considered a class of paramount importance, due to their widespread diffusion in a plethora of compounds.1 The diastereoselective and metal free, trichlorosilane-mediate reduction of imines, bearing different and removable chiral auxiliaries, in combination either with achiral bases or catalytic amounts of chiral Lewis bases, represents a feasible approach to afford immediate precursors of chiral APIs.2
In the present work, the carbon-nitrogen double bond reduction was successfully performed in batch and in flow mode, in high yields and almost complete stereocontrol.3 By this metal-free approach, the formal synthesis of Rasagiline and Tamsulosin was successfully accomplished in micro(meso) flow reactors, under continuous flow conditions. Chiral primary amines were obtained, either by a continuous flow hydrogenolysis, or directly out from the flow reactor after an in-line aqueous work up, depending on the chiral auxiliary group at the amine nitrogen atom.
References
1. Chiral Amine Synthesis: Methods, Developments and Applications (Ed.: T. C. Nugent), Wiley-VCH, Weinheim, 2010.
2. D. Brenna, M. Benaglia, R. Porta, S. D. Fernandes, A. J. Burke, Eur. J. Org. Chem, 2016, doi:10.1002/ejoc.201601268.
3. D. Brenna, M. Pirola, L. Raimondi, A.J. Burke, M. Benaglia, Bioorg. & Med. Chem., 2017, doi: http://dx.doi.org/10.1016/j.bmc.2017.01.023
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Keywords:
Flow chemistry; Stereoselective catalysis; Chiral amines; APIs synthesis; Trichlorosilane
Elenco autori:
M. Pirola, D. Brenna, L.M. Raimondi, A.J. Burke, M. Benaglia
Link alla scheda completa: