Efficient resolution of venlafaxine and mechanism study via X-ray crystallography.
Chirality
; 30(3): 268-274, 2018 Mar.
Article
em En
| MEDLINE
| ID: mdl-29232000
Numbers of resolving factors were investigated to improve resolution of venlafaxine 1. An effective resolving agent, O,O'-di-p-toluoyl-(R, R)-tartaric acid 2, was screened using similar method of 'Dutch resolution' from tartaric acid derivatives. The resolution efficiency was up to 88.4%, when the ratio of rac-1 and 2 was 1:0.8 in THF with little water (10:1 v/v). Enantiomerically pure venlafaxine was prepared with 99.1% ee in 82.2% yield. The chiral resolution mechanism was first explained through X-ray crystallographic study. One diastereomeric salt with well solubility forms a columnar supramolecular structure as the acidic salt (R)-1·2, while the other diastereomeric salt with less solubility forms a multilayered sandwich supramolecular structure by enantio-differentiation self-assembly as the neutral salt 2(S)-1·2. The water molecules play a key role in the optical resolution, as indicated by the special structures of the diastereomeric salts.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Revista:
Chirality
Assunto da revista:
BIOLOGIA MOLECULAR
/
QUIMICA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China