posted on 2016-02-19, 17:54authored byCristiano Bolchi, Marco Pallavicini, Laura Fumagalli, Valentina Straniero, Ermanno Valoti
(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.