1-Hydroxybenzotriazole → 9-[Oxo-(3,4,5-trimethoxyphenyl)-acetyl]-3-(4-phenyl-butyl)-3,9-diaza-bicyclo[3.3.1]nonane-2,4-dione

Participants

Reaction Conditions

Reaction Steps

3-(4-Phenylbutyl)-3,9-diaza-bicyclo[3.3.1]nonane-2,4-dione (Compound 14, 0.42 g, 1.47 mmol) and 2-oxo-3,4,5-trimethoxyphenylacetic acid (0.35 g, 1.47 mmol) were dissolved in CH2Cl2 (5 mL), and the solution was cooled to 0° C. HOBt (0.21 g, 1.54 mmol) was added, followed by EDC.HCl (0.30 g, 1.54 mmol) and TEA (0.15 g, 1.47 mmol). The reaction was allowed to reach room temperature and stirred for 5 hours. The volatiles were removed using a high-vacuum rotary evaporator. The residue was dissolved in EtOAc and washed with 10% citric acid solution (10 mL), followed by water (10 mL), saturated NaHCO3 (10 mL), and brine (10 mL). The combined organic layers were dried over Na2SO4 and were concentrated. Flash chromatographic purification of the residue (30% EtOAc/hexanes) gave Compound 15 as a pale-yellow solid (0.25 g, 34%, one isomer). mp=101-103° C.; Rf=0.32 (50% EtOAc/hexanes); IR: 2939, 2866, 1739, 1682, 1651, 1582, 1503, 1454, 1416, 1361, 1337, 1243, 1167, 1126, 1067, 991, 914, 862 cm−1; 1H NMR (major rotamer): δ 1.56-1.64 (m, 5H), 1.93-2.01 (m, 5H), 2.61-2.66 (m, 2H), 3.80-3.85 (m, 2H), 3.95 (s, 9H), 4.51 (brs, 1H), 5.46 (brs, 1H),7.14-7.29 (m, 7H); HRMS (M+H+): expected 509.2288, observed 509.2275; EA: calculated, C (66.13), H (6.34), N (5.51); found, C (66.00, H (6.37), N (5.50).

Provenance & Evidence