| 摘要 |
<p>The invention provides a novel method for the racemization of an optically active isomer, particularly the d-isomer, of a tetrahydroisoquinoline derivative of the formula: (I) wherein Ar is a trimethoxyphenyl group. This enables the enantiomorph (i.e. the d-isomer) which remains after subjecting a racemic modification of a tetrahydroisoquinoline derivative (I) to optical resolution and removing the desired optically active species (i.e. the ?-isomer), to be utilized. The racemization method comprises the steps of (a) acylating an optically active tetrahydroisoquinoline (I); (b) reacting the resulting optically active N-acyltetrahydroisoquinoline derivative (II) with an aralkyl halide; (c) hydrolyzing the resulting optically active N-acyltetrahydroisoquinoline derivative having protected hydroxy groups (III); (d) (1) subjecting the resulting optically active tetrahydroisoquinoline derivative having protected hydroxy groups (IV) to a halogenation reaction, followed by a dehydrohalogenation reaction, or (2) subjecting the optically active compound (IV) to nitrosation, followed by removal of hyponitrous acid; (e) reducing the resulting dihydroisoquinoline derivative having protected hydroxy groups (V); and then (f) subjecting the resulting racemic tetrahydroisoquinoline derivative having protected hydroxy groups (IV) to catalytic reduction to give the desired racemic modification of a tetrahydroisoquinoline derivative (I).</p> |
