The effective direct resolution procedure for the chiral drug bevantolol hydrochloride

The solubility of the chiral drug bevantolol hydrochloride1 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 of 1, 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.

Figure optionsDownload as PowerPoint slide

(R)-1-[[2-(3,4-Dimethoxyphenyl)ethyl]amino]-3-(3-methylphenoxy)-2-propanolC20H28ClNO4Ee = 99.8% (ee from HPLC)[α]D20 = +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 crystallizationAbsolute configuration: (R)

(R)-1,2-Epoxy-3-(2-methylyphenoxy)propaneC10H12O2[α]D20 = −12.9 (c 1.0, MeOH)Initial source of chirality: (S)-epichlorohydrinAbsolute configuration: (R)