[NH2:1][C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.[OH-].[Na+].[C:16](OC(=O)C)(=[O:18])[CH3:17].Cl>O>[C:16]([NH:1][C@H:2]([C:11]([OH:13])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1)(=[O:18])[CH3:17]To a solution of (−) tyrosine xxvii (2.50 g, 13.8 mmol) in NaOH (aq) (2 N, 7.59 mL, 15.2 mmol) was added H2O (6 mL). This vigorously stirred solution was cooled to 0° C., and acetic anhydride (3.25 mL, 3.52 g, 34.5 mmol) was added via syringe pump over 30 min. During this addition, excess NaOH (aq) (2 N, 34.5 mL, 69.0 mmol) was added in 10 portions. After the addition was complete, the reaction was warmed to room temperature and stirred for 45 min. The colorless solution was then carefully acidified to pH 2 with 6 N HCl (aq). After concentrating under reduced pressure, the resulting solid was extracted with 15% H2O in acetone (4×). The filtrate was concentrated under reduced pressure to afford a slightly yellow oil. The addition of H2O (1.5 mL) afforded N-acetyl tyrosine as a white precipitate (670 mg, 3.00 mmol, 22%) that was washed with H2O (3×). The washings were saved for later precipitations. To a solution of N-acetyl tyrosine (72 mg, 0.32 mmol) in 1:1 THF:H2O (1 mL) was added NaOH (aq) (1 N, 0.32 mL, 0.32 mmol). Benzyl chloroformate (49 μL, 58 mg, 0.34 mmol) was added followed by the dropwise addition of K2CO3 (aq) (2 N, 0.16 mL, 0.32 mmol). After stirring for 7 h at rt, the reaction was poured over H2O (10 mL) and carefully acidified to pH 2 with 6 N HCl (aq). The product was extracted from the water layer with EtOAc (3×), and the combined organic phase was separated, dried over MgSO4, filtered and concentrated under reduced pressure to afford the desired product xxix as a white solid (81 mg, 0.24 mmol, 75%).
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