Scalable, efficient process for the synthesis of ( R)-3,5-bistrifluoromethylphenyl ethanol via catalytic asymmetric transfer hydrogenation and isolation as a DABCO inclusion complex

( 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 (1 S,2 R)- cis-1-aminoindan-2-ol 10 and dichloro( p-...

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Bibliographic Details
Published inTetrahedron: asymmetry Vol. 14; no. 22; pp. 3581 - 3587
Main Authors Hansen, Karl B., Chilenski, Jennifer R., Desmond, Richard, Devine, Paul N., Grabowski, Edward J.J., Heid, Richard, Kubryk, Michele, Mathre, David J., Varsolona, Richard
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier Ltd 14.11.2003
Elsevier
Subjects
Chemistry
Chemistry, Inorganic & Nuclear
Chemistry, Organic
Chemistry, Physical
Physical Sciences
Science & Technology
AROMATIC KETONES
APREPITANT
RECEPTOR ANTAGONIST
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Summary:( 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 (1 S,2 R)- 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%. Graphic
ISSN:0957-4166
1362-511X
DOI:10.1016/j.tetasy.2003.08.043