Efficient Crystallization-Induced Dynamic Resolution of α-Substituted Carboxylic Acids
Citations Over TimeTop 19% of 2004 papers
Abstract
Herein we present a novel route to enantiomerically enriched chiral alpha-substituted carboxylic acids by crystallization-induced dynamic resolution (CIDR) of their diastereomeric salts with chiral amines. Thus, the racemic alpha-bromo acid 3 is converted reliably with (1R,2S)-2-amino-1,2-diphenylethanol in the presence of a catalytic amount of tetrabutylammonium bromide into its R-enantiomer 4 in 90% yield with 88% ee. Similarly, the racemic alpha-thiobenzoyl acid 5 could be resolved to 90% ee in 74% yield. Further enrichment to enantiomeric homogeneity could be achieved in both cases by crystallization. In a telescoped, two-step process, S-alpha-thiobenzoyl acid 6 (>or=99.6% ee) was prepared from the racemic bromide 3 in 63% yield. State-of-the-art parallel experimentation enabled rapid screening for suitable dynamic resolution conditions. Kinetic studies defined the influence of temperature, tetrabutylammonium bromide concentration, molarity, and solvent polarity on the resolution rate, product yield, and enantiomeric excess.
Related Papers
- → Dynamic changes in the triacylglycerol composition and crystallization behavior of cocoa butter(2020)20 cited
- → Alteration of Polymorphic Selectivity through Different Crystallization Mechanisms Occurring in the Same Crystallization Solution(2007)35 cited
- → Effect of the weather conditions during solution preparation on lysozyme crystallization(2017)1 cited
- New progress in research on crystallization technology(2001)