[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([C:14](O)=[O:15])[CH:11]=[C:10]([Cl:17])[C:9]=2[Cl:18])=[C:4]([F:19])[C:3]=1[O:20][CH3:21].S(Cl)([Cl:24])=O.C1(C)C=CC=CC=1>CN(C)C1C=CN=CC=1.CN(C)C=O.C(#N)C.CO>[Cl:17][C:10]1[C:9]([Cl:18])=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([O:20][CH3:21])[C:4]=2[F:19])[N:13]=[C:12]([C:14]([Cl:24])=[O:15])[CH:11]=1A mixture of 33.5 g (95 mmol) of 6-(4-chloro-2-fluoro-3-methoxyphenyl)-4,5-dichloro-2-pyridinecarboxylic acid, 10.2 mL (140 mmol) of thionyl chloride, 0.1 mL of N,N-dimethylforamide (DMF) and 200 mL of toluene was heated at 75° C. for 5 h. The reaction progress was monitored by conversion of the acid chloride to its methyl ester (one drop of reaction mixture added to 5 drops of a 10% wt methanol solution containing 4-(dimethylamino)pyridine, briefly heating to reflux, dilution with acetonitrile and injection). LC analysis indicated 8 area % remaining carboxylic acid and 3 area % of an unidentified closely following product. Another 5 mL of thionyl chloride and 0.1 mL of DMF was added, and heating was continued for an additional 2 h. After stirring at room temperature overnight, the reaction mixture was filtered to remove a small amount of an insoluble material. The filtrate was concentrated in vacuo, and toluene added twice and re-concentrated in vacuo to remove residual thionyl chloride. The white solid obtained (38.6 g) was dried in a vacuum oven at 40° C. to give 33.3 g of a white solid, mp 134-136° C. LC internal standard analysis (conversion to its methyl ester as described above) indicated 98.1 wt %. EIMS m/e (relative intensity) 369 (4Cl, 80), 332 (3Cl, 38), 304 (3Cl, 82), 269 (2Cl, 100), 254 (2Cl, 30), 226 (2Cl, 73), 191 (30), 156 (46); 1H NMR (400 MHz, CDCl3) δ 8.23 (s, 1 H), 7.32 (dd, J=8, 2 Hz, 1 H), 7.15 (dd, J=8, 7 Hz, 1 H), 4.02 (dd, J=1 Hz, 3 H); 19F NMR (376 MHz, 1H decoupled, CDCl3) δ 126.83.
불러오는 중…
