Continuous-Flow Synthesis of Tramadol from Cyclohexanone

Autor:	Timothy M. Monos, Jonathan N. Jaworski, John C. Stephens, Timothy F. Jamison
Rok vydání:	2020
Předmět:	Organic Chemistry Grignard reaction Cyclohexanone Flow chemistry Combinatorial chemistry chemistry.chemical_compound chemistry Yield (chemistry) Magnesium bromide medicine Reactivity (chemistry) Tramadol Mannich reaction medicine.drug
Zdroj:	Synlett. 31:1888-1893
ISSN:	1437-2096 0936-5214
Popis:	A multioperation, continuous-flow platform for the synthesis of tramadol, ranging from gram to decagram quantities, is described. The platform is segmented into two halves allowing for a single operator to modulate between preparation of the intermediate by Mannich addition or complete the fully concatenated synthesis. All purification operations are incorporated in-line for the Mannich reaction. ‘Flash’ reactivity between meta-methoxyphenyl magnesium bromide and the Mannich product was controlled with a static helical mixer and tested with a combination of flow and batch-based and factorial evaluations. These efforts culminated in a rapid production rate of tramadol (13.7 g°h–1) sustained over 56 reactor volumes. A comparison of process metrics including E-Factor, production rate, and space-time yield are used to contextualize the developed platform with respect to established engineering and synthetic methods for making tramadol.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::77f3d8f99937ea92cba1dff75eb4cb10 https://doi.org/10.1055/s-0039-1690884 Zobrazit plný text záznamu