Determination of the enantiomeric purity and the configuration of β-aminoalcohols using (R)-2-fluorophenylacetic acid (AFPA) and fluorine-19 NMR:: application to β-blockers

A method has been developed for determining the enantiomeric purity and the absolute configuration of beta-aminoalcohols of type ArOCH2CH(OH)CH2NHR (R = iPr, tBu). To determine enantiomeric purity, the amine function was first protected by a benzyl group, then the compound formed was esterified using the acid chloride of (R)-2-fluorophenylacetic acid (AFPA). The F-19 NMR analysis of the derivative obtained revealed the presence of two distinctly separate signals (similar to 2.5 ppm), the one for the RS-SR pair being the most deshielded. The configuration was determined directly on the aminoalcohol by using the acid. In stoichiometric conditions, when R = iPr, the amide function was obtained very preponderantly. The F-19 NMR spectrum of the amide presented four distinct signals when derivatization was carried out by means of a reaction between the (+/-)-beta-aminoalcohol and the (R)-AFPA. The extreme signals, which were over 3.5 ppm apart, did not belong to the same diastereomer. With R = tBu essentially the ester function was obtained. The first studies revealed the presence of two signals, though not as clearly separated as in the previous cases. Each experiment was simple to perform, and purification was not necessary. Mosher's acid gave unsatisfactory results in each case. (C) 2000 Elsevier Science Ltd. All rights reserved.