86939-40-4

Upstream product

• 86939-10-8 Indatraline 
• 1338922-82-9 (1R,3S)-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-inden-1-ol 
• 85662-98-2 3-(3',4'-dichlorophenyl)-indan-1-one 
• 95-50-1 1,2-dichloro-benzene 
• 621-82-9 Cinnamic acid 
• 86939-10-8 indatraline 
• 1422045-79-1 benzyl ((1R,3S)-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-inden-1-yl)carbamate 
• 1422045-78-0 (1R,3S)-1-(benzyloxy)-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene 

Relevant academic research and scientific papers

Enantiopurity determination of the enantiomers of the triple reuptake inhibitor indatraline

The present study describes the development of two approaches for the determination of the enantiopurity of both enantiomers of indatraline. Initially, a method was developed using different chiral solvating agents (CSAs) for diastereomeric discrimination regarding signal separation in 1H nuclear magnetic resonance (NMR) spectroscopy, revealing MTPA as a promising choice for the differentiation of the indatraline enantiomers. This CSA was also tested for its ideal molar ratio, temperature, and solvent. Optimized conditions could be achieved that made determination of enantiopurity for (1R,3S)-indatraline up to 98.9% enantiomeric excess (ee) possible. To quantify even higher enantiopurities, a high-performance liquid chromatography (HPLC) method based on a modified β-cyclodextrine phase was established. The influence of buffer type, concentration, pH value, percentage and kind of organic modifier, temperature, injection volume as well as sample solvent on chromatographic parameters was investigated. Afterwards, the reliability of the established HPLC method was demonstrated by validation according to the ICH guideline Q2(R1) regarding specificity, accuracy, precision, linearity, and quantitation limit. The developed method proved to be strictly linear within a concentration range of 1.25-1000 μM for the (1R,3S)-enantiomer and 1.25-750 μM for its mirror image that enables a reliable determination of enantiopurities up to 99.75% ee for the (1R,3S)-enantiomer and up to 99.67% ee for the (1S,3R)-enantiomer.

Asymmetric total synthesis of (+)-indatraline via diastereoselective amination of chiral ethers using chlorosulfonyl isocyanate

A concise asymmetric total synthesis of (+)-indatraline from readily available cinnamic acid is described. The key steps include Corey's oxazaborolidine-catalyzed asymmetric carbonyl reduction and a highly stereoselective amination of chiral benzylic ether with retention of stereochemistry using chlorosulfonyl isocyanate.