(S)-(+)-1-Phenyl-1,2,3,4-tetrahydroisoquinoline, which is the key intermediate in preparing the urinary antispasmodic drug solifenacin, was racemized in quantitative yield by a simple one-pot procedure through N-chlorination with trichloroisocyanuric acid, conversion of the N-chloroamine into the imine hydrochloride, and reduction of the imine double bond. The racemized amine was successfully resolved by d-(-)-tartaric acid obtaining (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline in 81% yield and with 96.7% ee and, from the crystallization mother liquors, the R enriched form. This was racemized by the same one-pot process and resolved by d-(-)-tartaric acid with the same efficiency. Such an approach to the racemization of 1-phenyl-1,2,3,4- tetrahydroisoquinoline can be industrially useful to recycle the waste R enantiomer resulting from the classical resolution used to obtain the S enantiomer on a large scale.
One-pot racemization process of 1-phenyl-1,2,3,4-tetrahydroisoquinoline : a key intermediate for the antimuscarinic agent solifenacin / C. Bolchi, M. Pallavicini, L. Fumagalli, V. Straniero, E. Valoti. - In: ORGANIC PROCESS RESEARCH & DEVELOPMENT. - ISSN 1083-6160. - 17:3(2013 Mar), pp. 432-437.
|Titolo:||One-pot racemization process of 1-phenyl-1,2,3,4-tetrahydroisoquinoline : a key intermediate for the antimuscarinic agent solifenacin|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||mar-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1021/op300343q|
|Appare nelle tipologie:||01 - Articolo su periodico|