Reaction Steps
To a solution of acid 124 (319 mg, 0.648 mmol) in DMF (5 mL) at 0° C. was added DIEA (226 μL, 130 mmol) and HBTU (246 mg, 0.648 mmol). After stirring for 15 min at 0° C., L-Phenylalanine benzyl ester hydrochloride (189 mg, 0.648 mmol) was added and stirring was continued while warming to room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with H2O and saturated aqueous NaCl then dried over Na2SO4. The crude product was purified by silica gel chromatography (gradient of 0 to 20% methanol in ethyl acetate) using a Biotage Horizons™ system. Compound 125 was obtained as a colourless liquid (150 mg, 32%). 1H NMR (400 MHz, CDCl3) δ 1.20 (t, J=7.0, 3H), 1.21 (t, J=7.0, 3H), 1.25-1.32 (m, 18H), 1.44 (s, 3H), 1.45 (s, 3H), 1.47 (s, 3H), 1.48 (s, 3H), 2.47-2.67 (m, 12H), 2.87 (bd, J=6.2, 4H), 3.89-4.18 (m, 12H), 5.03 (AB q, J=12.3, 2H), 5.05 (AB q, J=12.3, 2H), 5.88 (bt, J=8.8, 2H), 6.91-6.95 (m, 4H), 7.01 (ddd, J=3.5, 5.2, 8.7, 2H), 7.17-7.23 (m, 10H), 7.31-7.32 (m, 6H), 7.71 (ddd, J=1.8, 8.1, 11.6, 1H), 7.75 (ddd, J=1.8, 8.1, 11.6, 1H), 7.86 (t, J=14.0, 1H), 7.87 (t, J=14.0, 1H): 31P (162 MHz, CDCl3) δ 20.31 (d, J=4.9, 1 P), 20.37 (d, J=4.9, 1 P), 33.93 (bd, J=9.5, 2P).
