1,2-Dichloroethane → (S)-tert-Butyl 2-(2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(4-hydroxyphenyl)propanamido)acetate

Participants

Reaction Steps

Following the procedure as described in Example 24, except using Fmoc-Tyrosine (4.97 g, 12.32 mmol), tert-butyl 2-aminoacetate, 1.00HCl (2.168 g, 12.94 mmol), 1-hydroxy-7-azabenzotriazole (0.503 g, 3.70 mmol), CH2Cl2 (125 mL), N-methylmorpholine (1.490 mL, 13.55 mmol), EDC (2.61 g, 13.61 mmol) and stirring at room temp for 18 h, 6.76 g (quantitative yield) of the title compound is isolated as a white, sticky solid. Purification is done by BIOTAGE® Silica gel chromatography on a 90 g Thompson Single Step silica cartridge using a linear gradient from 100% CH2Cl2 to 50% EtOAc/CH2Cl2 over 10 column volumes. LC/MS (Condition A): ret. T=3.98 min, (M+H)+ 517.27. 1H NMR (500 MHz, methanol-d4) δ ppm 7.80 (2 H, d, J=7.63 Hz), 7.58 (2 H, d, J=7.32 Hz), 7.25-7.45 (4 H, m), 7.09 (2 H, d, J=7.93 Hz), 6.71 (2 H, d, J=8.24 Hz), 4.36 (2 H, dd, J=9.92, 6.26 Hz), 4.15-4.25 (2 H, m), 3.84 (2 H, d, J=1.53 Hz), 3.11 (2 H, dd, J=13.89, 4.73 Hz), 2.79 (2 H, dd, J=13.89, 9.92 Hz), 1.48 (9 H, s).

Provenance & Evidence