Article (Scientific journals)
Assessing inter- and intramolecular continuous-flow strategies towards methylphenidate (Ritalin) hydrochloride
Gerardy, Romaric; Winter, Marc; Vizza, Alessandra et al.
2017In Reaction Chemistry and Engineering
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Keywords :
Continuous-flow manufacturing; APIs; On-demand production
Abstract :
[en] The batch-to-flow translation of inter- and intramolecular strategies for the diastereoselective preparation of the active pharmaceutical ingredient threo-methylphenidate hydrochloride is presented. Both inter- and intramolecular strategies imply the telescoping of multiple processing steps and the generation of unstable diazo species under continuous-flow conditions. The intermolecular strategy relies on an unprecedented continuous-flow Rh-catalyzed intermolecular C–H carbene insertion, providing enriched threo-N-Boc methylphenidate in 38% or 19% isolated yield according to sequential or fully telescoped processes, respectively. Quantitative Boc-deprotection is carried out off-line. The intramolecular strategy relies on a continuous-flow thermal intramolecular C–H carbene insertion, providing enriched threo-methylphenidate hydrochloride in 70% isolated yield. A continuous-flow photochemical alternative is also presented. The critical step of the most promising intramolecular strategy is implemented on the mesoscale in a pilot-scale continuous-flow reactor.
Disciplines :
Chemistry
Author, co-author :
Gerardy, Romaric ;  Université de Liège > Département de chimie (sciences) > Center for Integrated Technology and Organic Synthesis - CiTOS
Winter, Marc;  Corning Reactor Technologies
Vizza, Alessandra;  Corning Reactor Technologies
Monbaliu, Jean-Christophe  ;  Université de Liège > Département de chimie (sciences) > Center for Integrated Technology and Organic Synthesis - CiTOS
Language :
English
Title :
Assessing inter- and intramolecular continuous-flow strategies towards methylphenidate (Ritalin) hydrochloride
Publication date :
2017
Journal title :
Reaction Chemistry and Engineering
eISSN :
2058-9883
Publisher :
Royal Society of Chemistry, Cambridge, United Kingdom
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Available on ORBi :
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