637036-77-2Relevant academic research and scientific papers
Process research and development of an NK-1 receptor antagonist. Enantioselective trifluoromethyl addition to a ketone in the preparation of a chiral isochroman
Caron, Stephane,Do, Nga M.,Sieser, Janice E.,Arpin, Patrice,Vazquez, Enrique
, p. 1015 - 1024 (2012/12/30)
CJ-17,493 (4) is a chiral NK-1 receptor antagonist. It was first prepared through a diastereoselective crystallization, then through chiral chromatography of a key intermediate, and ultimately via asymmetric synthesis. Multiple routes for the preparation of a key isochroman were demonstrated, and conditions for improved regioselectivity of a Friedel-Crafts acylation were identified. Cesium fluoride was found to be an acceptable initiator for the generation of a nucleophilic trifluoromethyl anion from CF3TMS. A cinchonine-derived catalyst was identified for the enantioselective addition of the trifluoromethyl group to the ketone, and it was found that the product of the addition would be converted directly to the isochroman by treatment with t-BuOK. A Duff reaction was used for the formylation, and the resulting aldehyde was coupled to amine 5 to afford CJ-17,493 (4).
Enantioselective addition of a trifluoromethyl anion to aryl ketones and aldehydes
Caron, Stephane,Do, Nga M.,Arpin, Patrice,Larivee, Alexandre
, p. 1693 - 1698 (2007/10/03)
The identification and development of a catalyst for the enantioselective nucleophilic addition of a trifluoromethyl anion to a ketone is described. An easily prepared cinchonine-derived catalyst was used in amounts as low as 4 mol% to afford enantiomeric
