Synthetic Route of 2734-70-5,Some common heterocyclic compound, 2734-70-5, name is 2,6-Dimethoxyaniline, molecular formula is C8H11NO2, 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.
Thymol (1.0 eq, 33.3mmol) and methyl 5-(chloromethyl)-2-furoate (1.0 eq, 33.3mmol) were dissolved in nitromethane (120mL, 0.2M). Aluminum trichloride (1.0 eq, 33.3mmol) dissolved in 25mL nitromethane was added to the above solution under nitrogen and heated to slow reflux over 10 min. The heat was turned off and left under nitrogen overnight. The reaction was quenched with 100mL of water and exctracted with dichloromethane. The crude mixture was evaporated to dryness and loaded onto plug chromatography column (1g crude/100g silica gel ratio). The column was eluted with 7 and 11percent ethyl acetate/hexanes to yield the desired product (2.9 g, 30percent). The ester was hydrolyzed to acid by lithium hydroxide in THF/MeOH/H2O (35/25/25). To a solution containing the 5-(4-hydorxy-5-isopropyl-2-methylbenzyl)-2-furoic acid (1.0eq, 3.6 mmol, 0.5M), and 2,6-dimethoxyaniline (1.0eq, 3.6mmol) were dissolved in DMF. To this mixture, HATU (1.0 eq, 3.6 mmol) and di-isopropyl ethyl amine (1.0 eq, 3.6 mmol) were added and stirred overnight. The mixture was heated for 10min at 45°C. The solution was placed into ethyl acetate (3x volume) and washed with water. The organic layer was evaporated to syrup and eluted on plug column chromatography (1:100 g crude/g silicagel) with 30 and 50 percent ethyl acetate/hexane to yield: N-(2,6-dimethoxyphenyl)-5-(4-hydroxy-5-isopropyl-2-methylbenzyl)-2furamide (820 mgs, 55percent yield). 1HNMR (CDCl3) 7.22ppm (1H, t, J=8.68 Hz), 7.08ppm (1H, d, J=3.40 Hz), 6.99ppm (1H,s), 6.64ppm (2H, d, J=8.68 Hz), 6.61ppm (1H, s), 5.97 ppm (1H, d, J=3.40 Hz), 3.95ppm, (2H,s), 3.85ppm, (6H,s), 3.17ppm, (1H,pentet, J=6.8 Hz) 2.23ppm, (3H,s), 1.25 ppm(3H,s), and 1.23ppm (3H, s).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 2,6-Dimethoxyaniline, its application will become more common.