Process for the preparation of nitrogen substituted aminotetralins derivatives

摘要

The present invention provides an alternative synthesis of N-substituted aminotetralines comprising resolution of N-substituted aminotetralins of formula (II), wherein R1, R2 and R3 are as defined for compound of formula (I).;

主权项

1. A process of manufacture of substantially optically pure 2-aminotetralins of formula will (I) by diastereoisomeric salt resolution of compound of formula (II),wherein salt resolution of compound of formula (II) is performed by
(i) reacting free base of compound of formula (II) with a substantially optically pure acid (IV) selected from the group consisting of (R)-2-methoxy-2-phenyl acetic acid, (R)-2-(2-chlorophenyl)-2-hydroxyacetic acid, (S)-2-hydroxy-3-phenylpropionic acid and (R)-(−)-2-(6-methoxy-2-naphthyl)-propionic acid, in a solvent to afford diastereoisomeric salts (V) and (V′); and (ii) converting (V) to (I) by
(1) crystallizing the resulting diastereoisomeric salt (V) of (i) in a solvent and(2) reacting said diastereoisomeric salt (V) of (ii)(1) with a mineral acid to afford the salt of compound of formula (I);wherein R1 and R2 are alkyl and R3 is hydrogen.