4-Hydroxybenzylamine

123-08-0

696-60-6

Preparative Example A: Synthesis of sodium 4-((2-aminopyridine-3-carbonyl)amino)methyl)phenol. To a solution of 4-hydroxybenzaldehyde (10 g, 81.9 mmol) in methanol (45 mL) was added nickel ryenne (3 g) and 7N aqueous ammonia solution (45 mL). The reaction mixture was stirred for 21 hours at room temperature under hydrogen atmosphere (1 atm). Upon completion of the reaction, the catalyst was removed by filtration through a diatomaceous earth pad and the filtrate was concentrated to afford 4-aminomethylphenol (10 g, quantitatively) as a light green solid. Subsequently, 2-aminonicotinic acid (3.0 g, 21.7 mmol) was dissolved in N,N-dimethylformamide (30 mL), 1-hydroxybenzotriazole (3.51 g, 26 mmol) and (3-dimethylaminopropyl)-ethylcarbodiimide (4.04 g, 26 mmol) were added, and the solution was cooled to 0°C. To this solution, 4-aminomethylphenol (3.0 g , 21.7 mmol) to a solution of N,N-dimethylformamide (20 mL) and the reaction mixture was stirred for 18 hours at room temperature. Upon completion of the reaction, the reaction solution was partitioned into brine and the organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was dissolved in ethyl acetate, filtered through silica gel and the filtrate was concentrated. The residue was dissolved in methanol (90 mL), 1N sodium hydroxide solution (17.8 mL, 17.8 mmol) was added and stirred at room temperature for 1.5 hours. The reaction solution was concentrated in vacuum to give 4-hydroxybenzylamine (5.66 g) as a light yellow solid.