29608-05-7

59507-44-7

29608-05-7

General procedure for the synthesis of 4-piperidine-1-methylaniline from 1-(4-nitrobenzyl)piperidine: To a solution of anhydrous THF (3 mL) with 4-nitrobenzyl chloride (1 mmol) was added 1-methylpiperazine or piperidine (1 mmol) and triethylamine (1.5 mmol, 0.21 mL) in sequence. The reaction mixture was stirred at 70 °C overnight. Upon completion of the reaction, extraction was carried out with dichloromethane and water. The organic phases were combined, dried with anhydrous Na2SO4 and concentrated under reduced pressure to remove the solvent. The residue was purified by column chromatography (eluent: hexane/ethyl acetate, 1:4) and structurally characterized by 1H NMR (see Supplementary Information). The purified product was dissolved in ethanol (10 mL) and PtO2 (0.01 g) was added under nitrogen protection. Hydrogenation was carried out in a Parr hydrogenation unit at 50 psi hydrogen pressure for 16 hours. At the end of the reaction, the catalyst was removed by filtration and the filtrate was concentrated in vacuum to give the target product 4-piperidine-1-methylaniline in quantitative yield.