Reaction Steps
Piperidine (85.0 mL, 85.6 mmol) was added to a suspension of 3-methoxy-4-propargyloxybenzaldehyde (163 g, 85.6 mmol) and 2-[(carboxyacetyl)amino]benzoic acid (182 g, 81.5 mmol) in toluene (1.0 L) and treated according to Procedure 2, acidifying with 50% AcOH. The crude product was recrystallised from EtOH (35 mL/g), filtered and washed with cold EtOH to afford (E)-2-[[3-(3-methoxy-4-propargyloxyphenyl)-1-oxo-2-propenyl]amino]benzoic acid (222 g, 77%) as a yellow crystalline solid; mp 191-193° C.; δH (400 MHz, DMSO-d6) 3.59 (t, J=2.4 Hz, 1H, HC≡C), 3.84 (s, 3H, OCH3), 4.84 (d, J=2.4 Hz, 2H, OCH2), 6.81 (d, J=15.6 Hz, 1H, CH═CHCO), 7.05 (d, J5′,6′=8.4 Hz, 1H, H5′), 7.16 (t, J3,4=J4,5=8.0 Hz, 1H, H4), 7.25 (d, J5′,6=8.4 Hz, 1H, H6′), 7.41 (s, 1H, H2′), 7.56 (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), 8.62 (d, J5,6=8.0 Hz, 1H, H6), 11.31 (s, 1H, NH), 13.57 (br S, 1H, CO2H); δC (100 MHz, DMSO-d6) 55.6, 55.9, 78.6, 79.1, 110.8, 113.5, 116.6, 120.4, 120.4, 122.2, 122.7, 128.2, 131.2, 134.0, 141.0, 141.5, 148.3, 149.3, 164.1, 169.5; HRMS (ESI) calculated for C2OH17NO5 [M+H]+ 352.1179. found 352.1187; vmax 755, 1010, 1140, 1253, 1502, 1582, 1657, 3278, 3522 cm−1.
