Reaction Steps
Piperidine (0.35 mL, 3.5 mmol) was added to a suspension of 4-methoxy-3-(but-2-ynyl)oxybenzaldehyde (0.72 g, 3.5 mmol) and 2-[(carboxyacetyl)amino]benzoic acid (0.72 g, 3.2 mmol) in toluene (10 mL) and treated according to Procedure 2, acidifying with 20% AcOH. (E)-2-{[3-(3-(But-2-ynyloxy)-4-methoxyphenyl)-1-oxo-2-propenyl]amino}benzoic acid (0.81 g, 69%) was obtained as a yellow crystalline solid; mp 170-171° C.; δH (400 MHz, DMSO-d6) 1.82 (t, J=2.0 Hz, 3H, CH3), 3.80 (s, 3H, OCH3), 4.80 (d, J=2.0 Hz, 2H, OCH2), 6.74 (d, J=15.6 Hz, 1H, CH═CHCO), 7.00 (d, 8.4 Hz, 1H, H5′), 7.16 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 7.27 (d, J5′,6′=8.4 Hz, 1H, H6′), 7.40 (s, 1H, H2′), 7.54 (d, J=15.6 Hz, 1H, CH═CHCO), 7.61 (t, J4,5=J5,6=8.0 Hz, 1H, H5), 8.00 (d, J3,4=8.0 Hz, 1H, H3), 8.61 (d, J5,6=8.0 Hz, 1H, H6), 11.31 (s, 1H, NH), 13.57 (br s, 1H, CO2H); δC (100 MHz DMSO-d6) 3.2, 55.6, 56.5, 74.7, 83.7, 111.9, 112.3, 116.6, 120.0, 120.3, 122.7, 123.2, 127.1, 131.2, 134.1, 141.1, 141.6, 146.9, 151.0, 164.1, 169.5; HRMS (ESI) calculated for C21H19NO5 [M+Na]+ 388.1155. found 388.12158; vmax 749, 1261, 1512, 1584, 1659, 2917, 3239, 3520 cm−1.
