Synthesis
General procedure: tert-butyl L-tyrosine (1.00 g, 4.21 mmol) and sodium bicarbonate (354 mg, 4.21 mmol) were suspended in 1,4-dioxane/water (1:1, 20 mL) with stirring. To this suspension was added 9-fluorenylmethyl-N-succinimidyl carbonate (1.42 g, 4.21 mmol), and the resulting mixture was stirred at room temperature for 18 hours. Upon completion of the reaction, the solvent was concentrated under reduced pressure to about 10 mL. cold 1N hydrochloric acid (50 mL) was added and the product was extracted with ethyl acetate (3 x 50 mL). The organic phases were combined, washed sequentially with water and saturated sodium chloride solution, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give the colorless solid product 83 (1.94 g, 100%), which could be used in the next reaction without further purification. The product was confirmed by 1H NMR (400 MHz, CDCl3): δ 1.43 (s, 9H), 2.97-3.06 (m, 2H), 4.21 (bt, J = 7.1 Hz, 1H), 4.33 (dd, J = 7.1, 10.5 Hz, 1H), 4.41-4.53 (m, 2H), 5.01 (bs, 1H), 5.30 (d, J = 8.2 Hz, 1H), 6.73 (d, J = 8.5 Hz, 2H), 7.00 (d, J = 8.5 Hz, 2H), 7.31 (t, J = 7.5 Hz, 2H), 7.40 (t, J = 7.5 Hz, 2H), 7.57 (dd, J = 3.3, 7.3 Hz, 2H), 7.76 (d, J = 7.5 Hz 2H).
References
[1] Patent: WO2010/19511, 2010, A2. Location in patent: Page/Page column 125-126
[2] Chemical Communications, 2011, vol. 47, # 15, p. 4439 - 4441
[3] Patent: CN104274839, 2017, B. Location in patent: Paragraph 0036; 0038; 0040; 0041
[4] Angewandte Chemie - International Edition, 2009, vol. 48, # 11, p. 2024 - 2026
[5] Tetrahedron Letters, 1995, vol. 36, # 27, p. 4733 - 4736
