A flask was charged with 3-benzyloxy-2-tert-butoxycarbonylaminopropionic acid (5.0 g, 16.9 mmoles), HATU (7.0 g, 18.6 mmoles) and DMF (5 mL). DIEA (8.8 mL, 50.7 mmoles) was added and the mixture was stirred for 15 minutes. 4-Phenoxyaniline (3.4 g, 18.6 mmoles) was added and the mixture was stirred at ambient temperature for 18 hours. The reaction mixture was partitioned between ethyl acetate and deionized water. The aqueous layer was separated and extracted twice with ethyl acetate. The combined extract was washed sequentially with 5% lithium chloride (3×10 mL), 1N sodium bicarbonate (2×10 mL), 5% citric acid (2×10 mL), deionized water (2×10 mL) and then brine (1×10 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude material was recrystallized from methanol to afford a white solid. The solid was combined with 4N hydrogen chloride in dioxane (25 mL). The mixture was stirred at ambient temperature for 18 hours. Volatiles then were removed under rotary evaporation. The resultant oil was partitioned between 1N sodium bicarbonate and ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined extract was washed with brine (2×10 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude was recrystallized from methanol to give 2-amino-3-benzyloxy-N-(4-phenoxyphenyl)propanamide (2 g, 5.47 mmoles, 33% yield), as an off-white solid. 1H-NMR (400 MHz, CDCl3): δ 9.55 (s, 1H), 7.60-7.50 (m, 2H), 7.40-7.27 (m, 5H), 7.08 (t, 1H), 7.01-6.95 (m, 3H), 4.57 (t, 2H), 3.85-3.70 (m, 3H), 1.97 (2, 2H). MS (D) for C22H22N2O3. found 363.0 (MH+).
