Process for the preparation of(1S,2R)-1-amino-2-indanol-(R,R)-tartrate methanol solvate

摘要

Process for the preparation of (1S,2R)-1-amino-2-indanol-(R,R)-tartrate methanol solvate, in which in a solvent a mixture of enantiomers of cis-1-amino-2-indanol reacts at an elevated temperature with (R,R)-tartaric acid and methanol and in which optically enriched (1S,2R)-1-amino-2-indanol-(R,R)-tartrate methanol solvate crystallizes out, after which the crystals are recovered, the recovery taking place at a temperature between 10 and 50 DEG C in the presence of 0-20 wt.% water relative to the amount of methanol plus solvent, on the understanding that if the reaction mixture is essentially free from water the recovery substantially takes place at a temperature between 30 and 50 DEG C. Preferably the reactants are at least in part contacted with each other at an elevated temperature and only methanol is used as solvent. Preferably the amount of (1S,2R)-1-amino-2-indanol applied is between 0.02 and 0.1 g per ml of solvent. The invention also relates to (1S,2R)-1-amino-2-indanol-(R,R)-tartrate methanol solvate crystals having a particle size larger than 95 mu m, expressed as DÄv, 0.9Ü, in particular those in which the enantiomeric excess of (1S,2R)-1-amino-2-indanol-(R,R)-tartrate relative to (1R,2S)-1-amino-2-indanol-(R,R)-tartrate is higher than 96%, as well as to application of (1S,2R)-1-amino-2-indanol-(R,R)-tartrate methanol solvate in the preparation of AIDS inhibitors, in particular indinavir sulphate.