Diastereoselective synthesis of cis-N-Boc-4-aminocyclohexanol with reductive ring opening method using continuous flow

Szabó, Balázs [Szabó, Balázs Péter (gyógyszervegyészet), szerző] Szerves Kémia és Technológia Tanszék (BME / VBK); Tamás, Bálint; Faigl, Ferenc ✉ [Faigl, Ferenc (Szerves kémia), szerző] Szerves Kémia és Technológia Tanszék (BME / VBK); Éles, János [Éles, János (gyógszerkémia, ár...), szerző] Richter Gedeon Nyrt.; Greiner, István [Greiner, István (Szerves kémia), szerző] Richter Gedeon Nyrt.

Angol nyelvű Szakcikk (Folyóiratcikk) Tudományos
Megjelent: JOURNAL OF FLOW CHEMISTRY 2062-249X 2063-0212 9 (1) pp. 13-17 2019
  • SJR Scopus - Chemistry (miscellaneous): Q1
Szakterületek:
  • Tudomány
The N-protected cis-4-aminocyclohexanol derivatives have proven to be valuable intermediates in the syntheses of active pharmaceutical ingredients (APIs). A novel continuous flow process for hydrogenation of N-protected 2-oxa-3-azabicyclo[2.2.2]oct-5-ene cycloadducts to the corresponding cis-4-aminocyclohexanols has been reported using H-Cube Pro. A > 99% selectivity towards the desired product was obtained using Raney nickel catalyst cartridge. Under carefully selected hydrogenation parameters the reduction could stop at the also valuable 2-oxa-3-azabicyclo[2.2.2] octane intermediate, with a selectivity of >99%. The N-protected 2-oxa-3-azabicyclo[2.2.2]oct-5-ene producing nitroso hetero-Diels–Alder cycloaddition was also accomplished in a flow system using an Omnifit column packed with MnO2. The two flow reactions were successfully merged in a system, thus the product was obtained in a multistep flow synthesis without any isolation or purification steps. Compared with the previously reported batch processes, the present multistep procedure facilitates an efficient cis selective preparation of numerous synthetically valuable 4-aminocyclohexanol derivatives.
Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
2024-11-09 23:22