preparation of m-fluorophenyl acetic acid_kain industrial additive

overview^[1]

fluorophenylacetic acid is an important intermediate and plays an irreplaceable role in the synthesis of pharmaceuticals, electronic materials, etc. for example, m-fluorophenylacetic acid can be used in the preparation of anti-inflammatory drugs. for another example, 2,4,5-fluorophenylacetic acid is a key intermediate for the preparation of sitagliptin, a diabetes treatment drug. for another example, 2,3-difluorophenylacetic acid can be used to prepare difluoronaphthol-based liquid crystal intermediates.

preparation^[1]

preparation of m-fluorophenyl acetic acid: add 350 grams of 32% hcl and 250 grams of 3-fluoroaniline into the reaction bottle, heat and stir until dissolved. cool to -5~5℃, add 20g tetramethylammonium chloride and 20g copper chloride. add dropwise an acetone solution containing 300 g of vinylidene chloride. maintaining the temperature, slowly add a solution containing 230g isopropyl nitrite and 200g acetone dropwise. the reaction was kept warm for 2 hours. the reaction is completed and quenched. dichloromethane was added for extraction and then distilled to obtain 398 g of 1-(2,2,2-trichloroethyl)-3-fluorobenzene. add 500g of water and 60g of p-toluenesulfonic acid to the three-necked flask under nitrogen protection. heat to 80~95℃. 300g of intermediate 1-(2,2,2-trichloroethyl)-3-fluorobenzene was added dropwise. after the dropwise addition is completed, the reaction is kept warm for 8 hours. the reaction is complete. the cooling system was added dropwise to ice water to quench. filter, wash with water, dry and recrystallize with dichloroethane to obtain 151.2g of pure m-fluorophenyl acetic acid, with hplc purity greater than 99wt%.

apply^[2]

m-fluorophenylacetic acid can be used to prepare m-fluorophenylacetyl chloride: add m-fluorophenylacetic acid, thionyl chloride and dimethylformamide in sequence to a clean three-necked flask, stir and heat to reflux, the temperature is 110°c. react for 3 to 5 hours. after the reaction is completed, the thionyl chloride is removed by distillation under normal pressure, and the burgundy product at 64°c/5mmhg is collected to obtain m-fluorophenyl acetyl chloride.

main reference materials

[1] cn201710170399.1 preparation method of fluorophenylacetic acid

[2] cn201410364152.x a kind of 4-(3-fluorophenyl)-2,2-dimethyl-5-(4-(methylthio)phenyl)furan-3(2h)-one preparation method