[Synthesis]
GENERAL STEPS: Potassium hydroxide (80.3 g, 1.22 mol) was dissolved in 200 mL of water under ice-bath cooling conditions, followed by the addition of D-tyrosine (100 g, 0.55 mol), controlling the internal temperature to be between 15-20 °C. Then copper sulfate pentahydrate (CuSO4-5H2O, 85.5 g, 0.34 mol) was added. The reaction mixture was heated to 60-65 °C with stirring and maintained at this temperature for 1 hour. After completion of the reaction, the mixture was allowed to cool to room temperature. N,N-dimethylformamide (DMF, 500 mL) was added to the mixture followed by slow dropwise addition of benzyl chloride (83.8 g, 76.28 mL, 0.66 mol) at room temperature. The reaction mixture was heated to 60 °C again and the reaction was stirred for 2 hours. During the reaction, the copper complex of O-benzyl-D-tyrosine precipitated as a gray solid. After the reaction mixture was cooled to room temperature, 300 mL of water was added to precipitate the free gray solid. The solid was collected by filtration and washed with water until the filtrate was colorless. The resulting wet cake of O-benzyl-D-tyrosine copper complex was stirred with methanol at reflux temperature for 1 h. After 1 h, the solid was filtered, washed with methanol, and dried in an oven at 65 °C. The dried copper complex was suspended in 1 L of water, heated to 50 °C, and the pH was adjusted by slowly adding 35% concentrated hydrochloric acid (90 mL). stirred for 2-3 h at room temperature. The resulting solid was collected by filtration, washed with 10% aqueous ammonia solution (300 mL) and finally dried in a vacuum oven at 65 °C to afford the target product (R)-2-amino-3-(4-(benzyloxy)phenyl)propionic acid (115 g, 77% yield). Results of mass spectrometry analysis: m/z 272 (M+1). |