Reaction Steps
Piperidine (0.24 mL, 2.4 mmol) was added to a suspension of 4-cyclohexylmethoxy-3-methoxybenzaldehyde (0.59 g, 2.4 mmol) and 2-[(carboxyacetyl)amino]benzoic acid (0.48 g, 2.1 mmol) in toluene (5.0 mL) and treated according to Procedure 2, acidifying with 1 M HCl. The crude product was recystallised from EtOH/water providing (E)-2-{[3-(4-cyclohexylmethoxy-3-methoxyphenyl)-1-oxo-2-propenyl]amino}benzoic acid (0.45 g, 51%) as a colourless crystalline solid; mp 207-210° C.; δH (400 MHz, DMSO-d6) 1.03 (m, 2H, CH2), 1.20 (m, 4H, CH2), 1.63-1.82 (m, 5H, CH2, CH), 3.79 (d, J=6.4 Hz, 1H, OCH2), 3.83 (s, 3H, OCH3), 6.76 (d, J=15.6 Hz, 1H, CH═CHCO), 6.96 (d, J5′,6′=8.4 Hz, 1H, H5′), 7.18 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 7.21 (d, J5′,6′=8.4 Hz, J2′,6′=1.8 Hz, 1H, H6′), 7.36 (s, J2′,6′=1.8 Hz, 1H, H2′), 7.55 (d, J=15.6 Hz, 1H, CH═CHCO), 7.62 (t, J4,5=J5,6=8.0 Hz, 1H, H5), 8.00 (d, J3,4=8.0 Hz, 1H, H3), 8.62 (d, J5,6=8.0 Hz, 1H, H6), 11.27 (s, 1H, NH), 13.58 (br s, 1H, CO2H); δC (100 MHz, DMSO-d6) 25.2, 26.0, 29.2, 37.0, 55.8, 73.3, 110.7, 112.6, 116.6, 119.7, 120.3, 122.6, 127.1, 131.1, 134.0, 141.0, 141.6, 149.1, 150.2, 164.2, 169.4; HRMS (ESI) calculated for C23H25NO5 [M+Na]+ 432.1781. found 432.1781; vmax 759, 1142, 1504, 1581, 1667, 2925, 3123 cm−1.
