PROCESS FOR THE PREPARATION OF (S)-(+)- OR (R)-(-)-10-HYDROXY DIHYDRODIBENZ[B,F]AZEPINES BY ENANTIOSELECTIVE REDUCTION OF 10,11-DIHYDRO-10-OXO-5H-DIBENZ[B,F]AZEPINES AND POLYMORPHS THEREOF
申请人:Biswas Sujay
公开号:US20130345198A1
公开(公告)日:2013-12-26
The present invention provides a novel process for the preparation of substituted optically pure (S)-(+)- or (R)-(−)-10-hydroxy-dihydrodibenz[b,f]azepines or derivatives thereof, starting from 10,11-dihydro-10-oxo-5H-dibenz[b,f]azepines using boronate esters or their derivatives. The present invention also provides use of thus prepared (S)-(+)- or (R)-(−)-10-hydroxy-dihydrodibenz[b,f]azepines for the preparation of their ester such as (S)-(−)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide or (R)-(+)-10-acetoxy-10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide. The present invention also provides novel solid state crystalline forms J
1
, J
2
, J
3
, J
4
and amorphous form of eslicarbazepine and the process for the preparation thereof. Also, the present invention provides novel solid state crystalline form and amorphous form of eslicarbazepine acetate and the process for the preparation thereof. The novel solid state forms of eslicarbazepine are useful for the preparation of derivatives of eslicarbazepine such as eslicarbazepine acetate.
本发明提供了一种新颖的方法,用于从10,11-二氢-10-氧代-5H-二苯并[b,f]氮杂环己烯起始,利用硼酸酯或其衍生物制备取代的光学纯(S)-(+)-或(R)-(-)-10-羟基-二氢二苯并[b,f]氮杂环己烯或其衍生物。本发明还提供了利用这样制备的(S)-(+)-或(R)-(-)-10-羟基-二氢二苯并[b,f]氮杂环己烯制备它们的酯,如(S)-(-)-10-乙酰氧基-10,11-二氢-5H-二苯并[b,f]氮杂环己烯-5-羧酰胺或(R)-(+)-10-乙酰氧基-10,11-二氢-5H-二苯并[b,f]氮杂环己烯-5-羧酰胺。本发明还提供了新颖的固态结晶形式J1、J2、J3、J4和eslicarbazepine的非晶态形式及其制备方法。此外,本发明提供了eslicarbazepine乙酸盐的新颖固态结晶形式和非晶态形式以及其制备方法。eslicarbazepine的新颖固态形式对于制备eslicarbazepine乙酸盐等eslicarbazepine的衍生物非常有用。