Scalable, efficient process for the synthesis of (R)-3,5-bistrifluoromethylphenyl ethanol via catalytic asymmetric transfer hydrogenation and isolation as a DABCO inclusion complex
| Autor: | Paul N. Devine, Michele Kubryk, Richard Desmond, Karl B. Hansen, Edward J. J. Grabowski, David J. Mathre, Varsolona Richard J, Richard M. Heid, Jennifer R. Chilenski |
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| Rok vydání: | 2003 |
| Předmět: |
chemistry.chemical_classification
Ketone Dimer Organic Chemistry Chiral ligand DABCO Transfer hydrogenation Combinatorial chemistry Catalysis Inorganic Chemistry Metal chemistry.chemical_compound chemistry visual_art visual_art.visual_art_medium Organic chemistry Physical and Theoretical Chemistry Enantiomeric excess |
| Zdroj: | Tetrahedron: Asymmetry. 14:3581-3587 |
| ISSN: | 0957-4166 |
| DOI: | 10.1016/j.tetasy.2003.08.043 |
| Popis: | (R)-3,5-Bistrifluoromethylphenyl ethanol 2, a key building block in the synthesis of aprepitant, has been synthesized from ketone 5 via catalytic asymmetric transfer hydrogenation using a simplified catalyst generation procedure. The process uses (1S,2R)-cis-1-aminoindan-2-ol 10 and dichloro(p-cymene)Ru(II)dimer 9 as the chiral ligand and metal source for the reduction. While the reduction provides 2 in 90–92% ee, an isolation of 2 as a 2:1 inclusion complex with DABCO was developed to allow for the upgrade of the enantiomeric excess to >99%. |
| Databáze: | OpenAIRE |
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