Fmoc-L-3-chlorotyrosine was synthesized as follows: 3-chlorotyrosine (113.5 g, 526 mmol) was added to a round-bottomed flask equipped with a mechanical stirrer and a temperature probe. 3-Chlorotyrosine was dissolved in a solution of dioxane: water = 2:1 (500 mL). Sodium carbonate (55.8 g, 526 mmol) was added and the solution was cooled to 0C in an ice bath. Fmoc-OSu (177.5 g, 526 mmol) was dissolved in dioxane (300 mL) and added to the solution in a single addition at 0 C. The reaction was stirred at 0 C for 5 hours. The reaction was allowed to warm to 0C. Room temperature overnight. Concentrate the reaction until a volume of 100mL is reached. Add 0.5 M potassium bisulfate until the pH is 3. Determine the pH using pH paper (0-14) placed directly in the mixture. determine the pH by comparing it to the graph included in the pH paper. extract the solution with ethyl acetate (3× 500 mL). The organic layers were combined and washed with water (500mL) and brine (500mL). The organic layer was then washed with sodium sulfate and concentrated to a constant 8 (under vacuum) to give Fmoc-L-3-chlorotyrosine as a light beige solid. (204 g., 95% pure) .
