Trifluoroacetic anhydride → N-methyl-4-nitrophenethylamine

Participants

Reaction Steps

25 g of 2-(4-nitrophenyl)-ethylamine hydrochloride were suspended in 500 ml of dichloromethane and reacted with 33 ml of triethylamine. 52 g of trifluoroacetic acid anhydride were added slowly dropwise to the reaction mixture at 0° C. After addition was complete, the reaction mixture was stirred for 2 hours at room temperature and then extracted by shaking twice, each time with 200 ml of 5% aqueous hydrochloric acid solution and twice with saturated aqueous sodium hydrogen carbonate solution. Then the dichloromethane phase was dried with sodium sulfate and concentrated. The residue was added to 500 ml tetrahydrofuran and reacted with 44 ml of methyl iodide. Then 10 g of sodium hydride were added batchwise and the reaction mixture was stirred for 2 hours at room temperature. After the reaction was complete, the reaction mixture was filtered and concentrated over silica gel. The residue obtained was purified by flash chromatography using 2:1 methyl-tert-butyl ether/cyclohexane as the eluent. The oil obtained was dissolved in 300 ml of methanol. 50 ml of a 20% aqueous sodium hydroxide solution were added to the solution and the mixture was stirred for 2 hours at room temperature. Then the main quantity of methanol was distilled off and 100 ml of water were added. The solution was shaken twice with 240 ml of dichloromethane each time. The organic phases were combined, dried, and concentrated. The remaining oily reaction product was purified by flash chromatography using dichloromethane/methanol/concentrated aqueous ammonia solution as the eluent. 8.9 g of N-[2-(4-nitrophenyl)-ethyl]-N-methylamine were obtained as an oil.

Provenance & Evidence