(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. [10.1021/op300343q]

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
2013-03

Abstract

(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.
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/219099
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