Reaction Steps
4-[4-(1-Ethoxycarbonyl-1-methyl-ethoxy)-phenyl] butyric acid (1.50 g, 5.04 mmol) was dissolved in ethyl acetate (10 mL). Oxalyl chloride (524 μL, 6.01 mmol) was added to this solution dropwise in the presence of a catalytic amount of N,N-dimethylformamide (30.1 μL, 0.41 mmol). Completion of acid chloride formation was verified by HPLC. This solution was then concentrated to remove residual oxalyl chloride and the resulting oil was redissolved in ethyl acetate (10 mL). This solution was then added dropwise to a suspension of N-propyl-1-phenylmethylhydrazine carboxamide methanesulfonate (1.52 g, 5.01 mmol) and pyridine (970 μL, 12.6 mmol) in ethyl acetate (15 mL) at 0° C. After stirring at 0° C. for 1 h, the solution was warmed to rt and washed with 1N HCl (2×20 mL) and 5% aq. NaHCO3 (2×20 mL) followed by sat'd aq. NaCl (20 mL). The organic layer was dried (MgSO4), filtered and concentrated to a yellow oil. The oil was purified by column chromatography (SiO2, 1:1 ethyl acetate:hexanes) to afford the title compound as a clear oil (1.42 g, 59%): 1H NMR (DMSO-d6, 60° C.) δ 9.51 (s, 1H), 7.20 (m, 5H), 7.01 (d, 2H, J=8 Hz), 6.71 (t, 1H, J=7 Hz), 4.55 (s, 2H), 4.17 (q, J=7 Hz), 3.00 (q, 2H, J=7 Hz ), 2.45 (t, 2H, J=2Hz ), 2.07 (t, 2H, J=2 Hz), 1.73 (quint, 2H, J=7 Hz), 1.48 (s, 6H), 1.40 (q, 2H, J=7 Hz ), 1.17 (t, 3H, J=7 Hz), 0.81 (t, 3H, J=7 Hz); 13C NMR (DMSO-d6) δ 174. 0, 172.0, 158.2, 153.8, 139.0, 135.8, 129.7, 128.84, 128.79, 127.6, 119.4, 79.2, 61.6, 51.3, 42.3, 34.3, 33.4, 27.1, 25.7, 23.7, 14.6, 11.9 ; IR (CHCl3) 3009, 1726, 1672, 1143 cm−1; Anal. Calcd. For C27H37N3O5: C, 67.05; H, 7.71; N, 8.69. Found: C, 66.65.; H, 7.63; N, 8.57.
