[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[CH:11][C:12]=2[NH2:13])=[CH:4][CH:3]=1.C1CCN2C(=NCCC2)CC1.[CH3:25][CH:26]([S:28](Cl)(=[O:30])=[O:29])[CH3:27].[NH4+].[Cl-]>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[CH:11][C:12]=2[NH:13][S:28]([CH:26]([CH3:27])[CH3:25])(=[O:30])=[O:29])=[CH:4][CH:3]=1Charge a double jacketed 20 L reactor equipped with mechanical stirrer and set under inert atmosphere of argon with 2-(4-Bromo-phenyl)-thiophene-3-ylamine (562 g, 2.21 mol) and CH2Cl2 (9.435 L). Obtain a clear solution. Add DBU (1.999 L) and cool the mixture to 9.4° C. Add propane-2-sulfonyl chloride (0.616 g) in 20 minutes maintaining the temperature below 25° C. Stir the reaction mixture 22 h at 20° C. After completion of reaction, cool the reaction mixture to 11° C. and add an aqueous solution of satd. aq. NH4Cl (7.65 L) cooled at 10° C. in 5 minutes. Heat the mixture to 20° C. and separate the aqueous phase. Wash the organic layer with 2N HCl (5.12 L), evaporate to dryness and take the residue into ethyl alcohol (800 g) . Heat the mixture until complete dissolution at 70° C. Cool the solution to 41° C. and add water (1384 mL). Stir the suspension overnight at 22° C., filter and wash two times with 254 mL of a 1/1 EtOH/H2O mixture. Dry the resulting beige solid under vacuum at 26° C. for 4 days to give propane-2-sulfonic acid[2-(4-bromo-phenyl)-thiophene-3-yl]-amide (688 g, 1.9 mol). 1H NMR (250 MHz, CDCl3): 1.25(d,6 H, J=6.9 H), 3.16 (hept, 1 H, J=6.9 Hz), 7.28(pseudo s, 2 H), 7.33(d, 2 H, J=8.5 Hz), 7.6(d, 2 H, J=8.5 Hz)
読み込み中…
