Methyl iodide → 4-[Methyl-(2-trifluoromethyl-phenyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

To a solution of 4-(2-trifluoromethyl-phenylamino)-piperidine-1-carboxylic acid tert-butyl ester (0.5 g, 0.00053 mole), in DMF (5 mL) was added, NaH (60% w/w dispersion in oil) (0.0696 g, 0.0029 mole) and the resulting mixture was stirred at ambient temperature for 10 minutes under an atmosphere of nitrogen. Methyl iodide (0.617 g, 0.00435 mole) was then added, and stirring was continued for 30 minutes at ambient temperature. The reaction mixture was quenched with aqueous 10% NH4Cl solution and the product was extracted with ether. The organic layer was washed with aqueous NaHCO3 solution followed by brine solution. The ether layer was then collected, dried over sodium sulfate and concentrated under reduced pressure to afford 0.5 g of 4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester that which was used in the next step without further purification. 4-[Methyl-(2-trifluoromethyl-phenyl)-amino]-piperidine-1-carboxylic acid tert-butyl ester obtained (0.5 g) was stirred in dioxane.HCl (5 mL) for 30 minutes. The reaction mixture was concentrated under reduced pressure to afford 0.36 g (88%) of methyl-piperidin-4-yl-(2-trifluoromethyl-phenyl)-amine hydrochloride which was used in the next step without further purification.

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