Acetic Acid → HCID 12003959, compound

Participants

Reaction Steps

The compound of Example 11 (560 mg), benzaldehyde (227.4 mg) and acetic acid (128.6 mg) in DMF was stirred under nitrogen at room temperature for 30 minutes. Na(OAc)3BH (568 mg) was added to the solution. The reaction was stirred under nitrogen at room temperature for overnight. The reaction was quenched by the addition of saturated NH4Cl solution (1 mL), followed by the addition of H2O (80 mL) for the attempt of making organic product crashed out of water layer. The solution was cloudy but no solid was formed. The solution was extracted by EtOAc (40 mL×3). The combined organic layer was washed by water (50 mL×2) and brine (50 mL×1), dried by Na2SO4 and concentrated to give crude product (466 mg), which was purified by silica gel chromatography conducted on CombiFlash™ Sq 16× (gradient: 100% CH2Cl2 to 10% MeOH in CH2Cl2) to give 3-(4-{3-[(R)-((2S,5R)-4-benzyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-[1,4]diazepan-1-yl)-propionic acid ethyl ester as white solid (290 mg; 44%). 1H NMR (300 MHz, CDCl3) δ 7.59-7.45 (m, 1H), 7.40 - 7.22 (m, 8H), 7.13 (dd, 1H, J=7.0, 7.0 Hz), 6.71 (m, 3H), 5.08 (s, 1H), 4.16 (q, 2H, J=7.0 Hz), 3.98 (m, 1H), 3.70 (m, 2H), 3.35 (m, 2H), 3.25 (m, 1H), 2.84 (m, 3H), 2.66 (m, 6H), 2.47 (m, 3H), 2.11 (m, 2H), 1.93 (m, 1H), 1.70 (m, 1H), 1.27 (t, 3H, J=7.0 Hz), 1.13 (bs, 3H), 1.06 (d, 3H, J=5.5 Hz).

Provenance & Evidence