Reaction Steps
Piperidine (0.19 mL, 1.9 mmol) was added to a suspension of 3-methoxy-4-(but-1-ynyloxy)benzaldehyde (0.39 g, 1.7 mmol) and 2-[(carboxyacetyl)amino]benzoic acid (0.39 g, 1.9 mmol) in toluene (5 mL) and treated according to Procedure 2, acidifying with 1M HCl. The crude product was recrystallised from EtOH/water providing (E)-2-[[3-(4-(but-3-ynyloxy)-3-methoxyphenyl)-1-oxo-2-propenyl]amino]benzoic acid (0.48 g, 75%) as a yellow crystalline solid; mp 178-180° C.; δH (400 MHz, DMSO-d6) 2.61 (dt, J=6.8, 2.4 Hz, 2H, CH2CCH), 2.86 (t, J=2.4 Hz, 1H, CCH), 3.81 (s, 3H, OCH3), 4.06 (t, J=6.8 Hz, 2H, OCH2), 6.77 (d, J=15.6 Hz, 1H, CH═CHCO), 6.98 (d, J5′,6′=8.0 Hz, 1H, H5′), 7.13 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 7.20 (d, J5,6′=8.0 Hz, 1H, H6′), 7.36 (s, 1H, H2′), 7.53 (d, J=15.6 Hz, 1H, CH═CHCO), 7.58 (t, J4,5=J5,6=8.0 Hz, 1H, H5), 7.97 (d, J3,4=8.0 Hz, 1H, H3), 8.59 (d, J5,6=8.0 Hz, 1H, H6), 11.25 (s, 1H, NH), 13.56 (br s, 1H, CO2H); δC (100 MHz, DMSO-d6) 19.6, 56.4, 67.2, 73.2, 82.0, 111.5, 113.6, 117.3, 120.8, 121.0, 123.2, 123.3, 128.4, 131.8, 134.7, 141.7, 142.2, 149.8, 150.1, 164.8, 170.1; HRMS (ESI) calculated for C21H19NO5 [M+H]+ 366.1336. found 366.1337; vmax 755, 1263, 1512, 1603, 1689, 3257, 3401 cm−1.
