These common heterocyclic compound, 363-51-9, name is 2-Chloro-6-fluoroaniline, 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. HPLC of Formula: C6H5ClFN
Example 4b N-(2′-Chloro-6′-fluoro-phenyl)-4-methylaniline A solution of 3.91 g 2-chloro-6-fluoroaniline in 4 nm of tetrahydrofuran and 35 ml of chlorobenzene is cooled down to -40 to -45 C. At this temperature, 5.09 g of titanium tetrachloride is added to the solution, followed by the addition of 5.0 g of 1-Methoxy-4-methylcyclohexa-1,4-diene. The reaction mixture is allowed to warm up to approx. -35 C. and stirred for 2 hours at this temperature. A solution of 10.18 g of iodine in 20 ml of tetrahydrofuran and 2.3 ml of acetic acid is then added drop-wise to the reaction mixture and the temperature was allowed to warm up to 0 C. The mixture was stirred for 1 hour at 0 C. and 16 hours at 25 C. Then 3.4 g of iodine is added to the reaction mixture and stirring is continued for additional 24 hours at 25 C. The reaction is finally quenched by pouring the reaction mixture onto a mixture of 250 ml of aeq. Sodium bisulfite (38-40%) and 400 ml of saturated aeq. sodium carbonate. The aqueous phase is extracted with ethyl acetate (1*200 ml and 2*100 ml), the ethyl acetate phases are unified and washed with 100 ml of water. The organic phase was dried over anhydrous sodium sulfate and evaporated in vacuo to give a yellow viscous liquid. The liquid was dissolved in hexane/t-butyl-methylether and the solution was filtered over silica gel to obtain, after evaporation of the solvent, 4.33 g of crude product. The product can be used directly in the next step. Alternatively, it can be purified e.g. by column chromatography on silica gel with hexane/t-butyl-methylether (9:1) as eluent to yield pure N-(2-Chloro-6′-fluoro-phenyl)-4-methylaniline. 1H-NMR (DMSO-d6, 500 MS, 300K) delta 2.17 (s, 3H, CH3); 6.53 [dd, J=8.5 Hz, JH-F=1.5 Hz, 2H, HC (2) and HC (6)], 6.94 [d, J=8.0 Hz, 2H HC (3) and HC (5)], 7.16 [ddd, J=8.0 Hz, JH-F=6.0 Hz, 1H, HC (4′)], 7.25 [ddd, J=8.0, 1.5 Hz, JH-F=8.0, 1H, HC (5′)]; 7.34 [ddd, J=8.0, 1.5 Hz, JH-F, 1.5, 1H, HC (3′)]; 7.63 (s, 1H, NH). MS (EI) m/z 235 (100, M+), 200 (35, (M-Cl)+), 185 (55)
The synthetic route of 2-Chloro-6-fluoroaniline has been constantly updated, and we look forward to future research findings.
Reference:
Patent; Acemoglu, Murat; Allmendinger, Thomas; Calienni, John Vincent; Cercus, Jacques; Loiseleur, Olivier; Sedelmeier, Gottfried; Xu, David; US2008/249318; (2008); A1;,
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