Reference of 450-89-5, As we all know, there are many different methods for the synthesis of a compound, and people can choose the synthesis method that suits their own laboratory according to the actual situation. 450-89-5 name is 2-Chloro-5-fluoroanisole, This compound is widely used in many fields, so it is necessary to find a new synthetic route. The downstream synthesis method of this compound is introduced below.
To a solution of 1-chloro-4-fluoro-2-methoxy-benzene (12.9 g, 80 mmol) in 1,2- dichloroethane (80 mL) at room temperature, CHLOROACETYL chloride (7.7 mL, 96 MMOL) and aluminium trichloride (21.4 g, 0.16 MMOL) were added. The solution was heated to 70C and stirred at this temperature for 3h under nitrogen. After cooling to room temperature, the reaction mixture was carefully poured onto crushed ice and extracted with DCM (2 x 150 mL). Washing of the organic layers with brine (200 mL) followed by drying (NA2SO4) and removal of the solvent in vacuo afforded a crude which was purified by flash chromatography eluting with 20% cyclohexane in ethyl acetate. The oil collected (8 g) was a mixture containing the title compound together with 2-CHLORO-4-(2-CHLORO-ACETYL)-5-FLUORO-PHENYL CHLOROACETATE. The mixture (7.8 g) was dissolved in methanol (100 mL) and a 2M aqueous solution of sodium carbonate (45 mL) was added. The solution was stirred at room temperature for 1H then the organic solvent was removed under vacuum and the remaining solution was acidified with a 5% aqueous solution of HCI, extracted with DCM (120 mL), washed with brine (80 mL) and dried (NA2SO4). Removal of the solvent in vacuo afforded the title compound (D37) as a brown solid (6.8 g, 38%). MS; (EI) M/Z : 222 [M] +. C8H5CI2FO2 requires 222. ‘H-NMR (500 MHz, DMSO-D6) 8 : 11.8 (bs, 1H), 7.87 (d, 1H), 6.83 (d, 1H), 4.94 (d, 2H)
At the same time, in my other blogs, there are other synthetic methods of this type of compound, 2-Chloro-5-fluoroanisole, and friends who are interested can also refer to it.
Reference:
Patent; GLAXO GROUP LIMITED; WO2004/46124; (2004); A1;,
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics