1 research outputs found
The Development of an Asymmetric Hydrogenation Process for the Preparation of Solifenacin
The successful development of a catalytic imine asymmetric
hydrogenation
process for the reduction of the hydrochloride salt of 1-phenyl-3,4-dihydroisoquinoline
to 1-(<i>S</i>)-phenyl-1,2,3,4-tetrahydroisoquinoline is
described. This represents a novel approach to the key intermediate
in preparing the urinary antispasmodic drug solifenacin, (1<i>S</i>)-(3<i>R</i>)-1-azabicyclo[2.2.2]oct-3-yl-3,4-dihydro-1-phenyl-2(1<i>H</i>)-isoquinoline carboxylate. Suitable reaction conditions
were identified through an extensive screen of catalysts and combination
of solvents and additives. The best reaction conditions: [Ir(COD)Cl]<sub>2</sub>-(<i>S</i>)-P-Phos, molar substrate to catalyst
ratio (S/C) of >1000/1, THF, 1–2 equiv of H<sub>3</sub>PO<sub>4</sub>, 60 °C, 20 bar H<sub>2</sub>, were reproduced on a 200
g scale (95% isolated yield, 98% ee and >99% HPLC product purity)