37% |
With 2-Picolinic acid; potassium phosphate; copper(l) iodide; In dimethyl sulfoxide; at 90℃;Sealed tube; |
A mixture of commercial 8-hydroxyjulolidine 9-carboxaldehyde(638 mg, 2.94 mmol, 1.7 equiv.), N-Boc-3-iodoaniline (552 mg, 1.73mmol, 1 equiv.), finely ground K3PO4 (732 mg, 3.45 mmol, 2 equiv.),CuI (33 mg, 0.17 mmol, 0.1 equiv.) and picolinic acid (43 mg, 0.35mmol, 0.2 equiv.) in dry DMSO (4.2 mL) was heated in a sealed tube at 90 C overnight. The reaction was checked for completion by TLC (DCM 100%) and diluted with EtOAc. Then, the resulting mixture was washedwith deionized H2O three times and brine, dried over anhydrous MgSO4,filtered and concentrated under reduced pressure. The resulting residuewas purified by flash-column chromatography over silica gel (eluent:step gradient of EtOAc in heptane from 10% to 20%) to obtained thecompound 8 (247 mg, 0.63 mmol, yield 37%) as a yellow amorphouspowder. IR (ATR, neat): 656, 685, 726, 768, 832, 860, 905, 956, 980,1006, 1049, 1070, 1129, 1148, 1197, 1235, 1269, 1281, 1306, 1341,1366, 1390, 1454, 1492, 1519, 1589, 1652, 1722, 2058, 2249, 2843,2933, 2843, 3294; 1H NMR (500 MHz, CDCl3): 9.82 (s, 1H, H-aldehyde),7.42 (d, J 1.0 Hz, 1H), 7.13 (t, J 8.2 Hz, 1H), 7.04 (d, J 8.2Hz, 1H), 6.89 (t, J 2.2 Hz, 1H), 6.53 (s, 1H), 6.46-6.42 (m, 1H), 3.28(dd, J 6.6 Hz, J 4.9 Hz, 2H), 3.23 (dd, J 6.6 Hz, J 4.9 Hz, 2H),2.75 (t, J 6.3 Hz, 2H), 2.50 (t, J 6.3 Hz, 2H), 2.03-1.91 (m, 2H),1.89-1.78 (m, 2H), 1.48 (s, 9H, CH3-Boc); 13C NMR (126 MHz, CDCl3): 187.5, 159.8, 154.3, 152.6, 149.4, 140.1, 130.2, 126.5, 118.3, 117.1,112.6, 112.1, 109.4, 105.7, 80.8, 50.2, 49.8, 28.4, 27.5, 21.4, 21.1, 20.6;HPLC (system A): tR 5.5 min (purity 97% at 260 nm); LRMS (ESI,recorded during RP-HPLC analysis): m/z 353.2 [M - tBu H] (100),409.4 [M H] (60), 817.5 [2 M H] (5), calcd for C24H29N2O4409.2; LRMS (ESI-, recorded during RP-HPLC analysis): m/z 453.3 [M FA - H]- (100), calcd for C25H29N2O6 453.2. |