Reference of 95-81-8, A common heterocyclic compound, 95-81-8, name is 2-Chloro-5-methylaniline, molecular formula is C7H8ClN, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
EXAMPLE 62 N-((4-Chlorophenyl)methyl)-4-hydroxy-5-methyl-3-quinolinecarboxamide [] A mixture of 2-chloro-5-methylaniline (2.83 g) and diethyl ethoxymethylenemalonate (4.04 mL) is heated at 135 C for 2 h. The resulting mixture is diluted with diphenyl ether (40 mL) and heated to reflux with a Dean-Stark trap for 1 h. The mixture is allowed to cool to rt and is then poured into hexane (50 mL). The solid is filtered and is washed with hexane (20 mL) and hexane/diethyl ether (1/1, 2 x 30 mL) to afford 4.89 g of the 8-chloro-6-methyl-quinolinecarboxylate ethyl ester. The ethyl ester (2.0 g) is dissolved in acetic acid (150 mL) along with NaOAco3 H2O (1.12 g) and 5% palladium on carbon (750 mg). The mixture is placed under hydrogen pressure (28 psi) in a Parr hydrogenator for 3 h. The mixture is filtered through a plug of celite, concentrated in vacuo, and suspended in water (10 mL). The crude product is filtered, washed with water, and recrystallized (DMF) to afford 964 mg of the 5-methyl-quinolinecarboxylate ethyl ester. The resulting ester (463 mg) and 4-chlorobenzylamine (2.43 mL) are heated at 190 C for 1 h. The resulting mixture is diluted with toluene (5 mL) and allowed to cool to rt affording a white solid. The crude product is filtered, washed with toluene (2 mL) followed by hexane (4 mL), and then recrystallized successively from acetic acid/water then ethyl acetate to afford 426 mg of the title compound as a white solid. Physical characteristics are as follows: Mp 205-6 C.1H NMR (300 MHz, DMSO) delta 12.50, 10.46, 8.64, 7.55, 7.47, 7.37, 7.15, 4.51, 2.83.13C NMR (100 MHz, DMSO) delta 179.47, 165.26, 143.30, 141.17, 140.60, 139.33, 132.26, 131.80, 129.75, 128.77, 127.97, 125.04, 117.56, 112.18, 41.84, 24.21IR (mull) 3404, 2924, 2855, 1645, 1628, 1604, 1574, 1545, 1498, 1467, 1459, 1342, 1224, 1170, 1097, 1016, 816, 783, 75 cm-1.HRMS (FAB) Found, 326.0803.MS (ESI-) for C18H15ClN2O2m/z 325 (M-H)-.
The synthetic route of 95-81-8 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Pharmacia & Upjohn Company LLC; EP1042295; (2005); B1;,
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