Triethylamine → 1-{2-[(6-Aminohexanoyl)(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate

Participants

Reaction Steps

1-[2-(Methylamino)ethyl]piperidin-4-yl biphenyl-2-ylcarbamate (500 mg, 1.41 mmol) was dissolved in methylene chloride (5 mL), triethylamine (0.236 mL, 1.70 mmol) and 6-bromohexanoyl chloride (0.232 mL, 1.56 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 20 minutes. Water was added to the reaction mixture, the reaction mixture was extracted with ethyl acetate (×3), and the organic layer was washed with saturated sodium chloride solution. The organic layer was dried with anhydrous sodium sulfate, then the solvent was evaporated under reduced pressure, the resulting residue was dissolved in N,N-dimethylformamide (3 mL), sodium azide (110 mg, 1.69 mmol) was added, and the mixture was stirred at 60° C. for 5 hours. The reaction mixture was diluted with ethyl acetate, and then the organic layer was washed successively with water (×3) and saturated sodium chloride solution. The organic layer was dried with anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. Triphenylphosphine (555 mg, 2.12 mmol) and water (38 μL, 2.12 mmol) were added to a solution of the resulting residue in tetrahydrofuran (14 mL) under ice cooling, and the mixture was stirred overnight at room temperature. The solvent of the reaction mixture was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=100:0→10:1, v/v) to give the title compound (493 mg; yield, 75%) as a yellow oily substance.

Provenance & Evidence