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

Abstract

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° 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° 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 μm, expressed as D[v, 0.9], in particular those in which the enantiomeric excess of (1S,2R)-1-amino-2-indanol-(R,R)-tartrate relative to (1S,2R)-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.

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