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Analytical and semi‐preparative HPLC enantioseparation of novel pyridazin‐3(2 H )‐one derivatives with α‐aminophosphonate moiety using immobilized polysaccharide chiral stationary phases
Author(s) -
Zhang Yuping,
Zhang Xiaoyan,
Zhou Jun,
Song Baoan,
Bhadury Pinaki S.,
Hu Deyu,
Yang Song
Publication year - 2011
Publication title -
journal of separation science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.72
H-Index - 102
eISSN - 1615-9314
pISSN - 1615-9306
DOI - 10.1002/jssc.201000705
Subject(s) - chemistry , enantiomer , moiety , dichloromethane , chromatography , hexane , high performance liquid chromatography , chiral column chromatography , organic chemistry , solvent
The direct HPLC enantioseparation of a novel series of chiral pyridazin‐3(2 H )‐one derivatives with α ‐ aminophosphonate moiety was performed on two immobilized polysaccharide chiral stationary phases (Chiralpak IA, Chiralpak IC) using n ‐hexane ( n ‐Hex)/dichloromethane (DCM) mobile phase with 5% alcohol additive. Good baseline separation of the enantiomers was achieved using amylose tris ‐(3,5‐dimethylphenylcarbamate) chiral stationary phases (Chiralpak IA) on analytical scale. The analytical method was further scaled up to semi‐preparative loading to obtain small amounts of both the enantiomers of pyridazin‐3(2 H )‐one derivative. The semi‐preparative resolution of all compounds was successfully achieved with n ‐hexane/dichloromethane/ethanol (EtOH) as mobile phase using a semi‐preparative Chiralpak IA column. The first fractions were isolated with purities of >99.9% (enantiomeric excess (e.e.), and the second fractions were obtained with purities of >98.2% (enantiomeric excess). The assignment of the absolute configuration was established for the F1 fraction of compound a‐2 by single‐crystal X‐ray diffraction method.