Resolution of N-methylamphetamine enantiomers with tartaric acid derivatives by supercritical fluid extraction

Abstract

The resolution of N-methylamphetamine (MA) was carried out with the resolution agents O, O′-dibenzoyl-(2 R,3 R)-tartaric acid monohydrate (DBTA) and O, O′-di- p-toluoyl-(2 R,3 R)-tartaric acid (DPTTA). After partial diastereomeric salt formation, the unreacted enantiomers were extracted by supercritical fluid extraction (SFE). The effects of resolution agent molar ratio to the racemic mixture (mr), extraction pressure ( P) and temperature ( T) on the resolution efficiency were studied. The best chiral separation was obtained at a quarter of an equivalent resolution agent molar ratio for both resolution agents. Extraction conditions [pressure (100–200 bar), temperature (33–63 °C)] did not influence the resolution efficiency, which makes the enantiomer separation robust. In one extraction step, both enantiomers can be produced with high enantiomeric excess (ee) and remarkable yield ( Y). Using DBTA as a resolution agent ee E=83%, Y E=45% for the extract and ee R=82%, Y R=42% for the raffinate were obtained.