The effective direct resolution procedure for the chiral drug bevantolol hydrochloride. Issue 9 (1st June 2016)

• Record Type: Journal Article
• Authors: Bredikhina, Zemfira A.; Antonovich, Olga A.; Zakharychev, Dmitry V.; Bredikhin, Alexander A.
• Is Part Of: Tetrahedron, asymmetry. Volume 27:Issue 9/10(2016)
• Page Start: 397
• Page End: 403
• Publication Date: 2016-06-01
• Subjects: Asymmetry (Chemistry) -- Periodicals; 547.005
• DOI: 10.1016/j.tetasy.2016.03.012
• Languages: English
• ISSNs: 0957-4166

Abstract

Graphical abstract: Abstract: The solubility of the chiral drug bevantolol hydrochloride 1 in water and the azeotropic mixture ethanol–water has been investigated. It was found that rac -1 meets the requirements of Meyerhoffer's rule, so it was possible to reduce the ternary diagram, describing the solubility of1, to a pseudo binary form, which facilitates the analysis of crystallization processes caused by temperature changes. On this basis, the effective and robust resolution procedure of racemic bevantolol hydrochloride by a preferential crystallization approach has been realized successfully. Abstract : ( R )-1-[[2-(3, 4-Dimethoxyphenyl)ethyl]amino]-3-(3-methylphenoxy)-2-propanol: C20 H28 ClNO4 Ee = 99.8% ( ee from HPLC) [ α ]D 20 = +19.3 ( c 1.1, EtOH) Initial source of chirality: resolution of racemic 1-[[2-(3, 4-dimethoxyphenyl)ethyl]amino]-3-(3-methylphenoxy)-2-propanol by preferential crystallization Absolute configuration: ( R ) Abstract : ( R )-1, 2-Epoxy-3-(2-methylyphenoxy)propane: C10 H12 O2 [ α ]D 20 = −12.9 ( c 1.0, MeOH) Initial source of chirality: ( S )-epichlorohydrin Absolute configuration: ( R )