Crystallization-based resolution of 1, 4-benzodioxane-2-carboxylic acid enantiomers via diastereomeric 1-phenylethylamides. Issue 18 (4th May 2016)

• Record Type: Journal Article
• Authors: Fumagalli, Laura; Bolchi, Cristiano; Bavo, Francesco; Pallavicini, Marco
• Is Part Of: Tetrahedron letters. Volume 57:Issue 18(2016)
• Page Start: 2009
• Page End: 2011
• Publication Date: 2016-05-04
• Subjects: 1-Phenylethylamine -- 1, 4-Benzodioxane-2-carboxylic acid -- Covalent diastereomers -- Resolution; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2016.03.100
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: rac -1, 4-Benzodioxane-2-carboxylic acid is amidified with ( R )-1-phenylethylamine. The two diastereomeric amides are resolved by precipitation of the S, R stereoisomer. The R, R diastereoisomer is isolated from the mother liquors by chromatography. Hydrolysis of the two amides yields 1, 4-benzodioxane-2-carboxylic acid enantiomers. The resolving agent ( R )-1-phenylethylamine is quantitatively recovered. Abstract: Unlike the diastereomeric 1-phenylethylammonium salts, the diastereomeric N -1-phenylethylamides of ( S )- and ( R )-1, 4-benzodioxane-2-carboxylic acid show significant differences in fusibility and solubility so as to be efficiently resolved by precipitation of the less soluble diastereomer (>98% de), while chromatographic purification of the unprecipitated fraction affords the more soluble one (>99% de). Overall, 95% of the former and 80% of the latter are recovered. The hydrolysis of the two resolved amides provides the two acid enantiomers and the resolving amine in quantitative yield and with unchanged stereoisomeric purity.