Determination of the enantiomeric purity and the configuration of beta-aminoalcohols using (R)-2-fluorophenylacetic acid (AFPA) and fluorine-19 NMR: application to beta-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 firs t protected by a benzyl group, then the compound formed was esterified usin g the acid chloride of (R)-2-fluorophenylacetic acid (AFPA). The F-19 NMR a nalysis 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 aminoalc ohol by using the acid. In stoichiometric conditions, when R = iPr, the ami de function was obtained very preponderantly. The F-19 NMR spectrum of the amide presented four distinct signals when derivatization was carried out b y 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 cle arly separated as in the previous cases. Each experiment was simple to perf orm, and purification was not necessary. Mosher's acid gave unsatisfactory results in each case. (C) 2000 Elsevier Science Ltd. All rights reserved.