Reaction Steps
To a cooled (0° C.) solution of SOCl2 (0.51 mL, 7.0 mmol) in dry toluene (2 mL) under an argon atmosphere was added a solution of 2-(E-2-carboxymethylethenyl)-3-[8-(4-methoxyphenyl)octyloxy]-6-hydroxymethylpyridine (300 mg, 0.70 mmol) in toluene (5 mL). After 5 minutes the cooling bath was removed and the reaction was stirred for 2 hours at room temperature. The toluene and excess SOCl2 were evaporated. To this was added dry DMF (0.90 mL), 3-aminophenol t butylcarbamate (209 mg, 1.0 mmol), and anhydrous Cs2CO3 (1.63 g, 5.0 mmol). The reaction was heated at 90° C. under an atmosphere of argon for 2 hours. Upon cooling to room temperature the reaction was diluted with EtOAc and washed with H2O, 10% NaOH, H2O, and brine and dried (MgSO4). Purification by flash column chromatography (silica, EtOAc:hexane:CH2Cl2, 7:63:30) yielded a colorless oil: 1H NMR (250 MHz, CDCl3) δ8.09 (d, J=15.7 Hz, 1H, olefin), 7.44 (d, J=8.6 Hz, 1H, aryl), 7.15 (m, 5H, aryl), 7.05 (d, J=15.7 Hz, 1H, olefin), 6.90 (m, 1H, aryl), 6.82 (d, J=8.6 Hz, 2H, aryl), 6.65 (m, 1H, aryl), 6.51 (s, 1H, NH), 5.12 (s, 2H, CH2 -O), 4.0 (t, J=6.5 Hz, 2H, O-CH2), 3.81 (s, 3H, methyl ester), 3.78 (s, 3H, OMe), 2.54 (t, J=7.6 Hz, 2H, benzylic), 1.88 (m, 2H, CH2), 1.51 (s, 9H, t butyl), 1.46 (m, 10H, aliphatic).
