p-Toluenesulfonic acid → HCID 58699966、化合物

To a solution of (±)-4-oxo-3-(trifluoromethyl)piperidine-1-carboxylic acid tert-butyl ester (2b) (1 equiv.) in toluene is added (R)-(+)-α-methylbenzylamine (1 equiv.) and catalytic amount of p-toluenesulfonic acid. The solution is heated to reflux under a Dean-Stark apparatus. After 12 hr, the reaction is cooled to RT, washed with 10% aqueous NaHCO3, dried over Na2SO4, and concentrated in vacuo. The residue is dissolved in EtOH and NaBH4 (1 equiv.) is added. After 12 h, the reaction is concentrated and the residue is dissolved in 1 N HCl. The solution is neutralized with 6 N NaOH and extracted with EtOAc. The organic fraction is dried over Na2SO4 and concentrated under vacuum. The crude product is purified by chromatography on silica gel to afford the title compound. The three other diastereomers are also separated.