3-Fluoro-4-methylbenzonitrile

white to light yellow crystal powder

A 50 mL four-necked flask was charged with 1.0 g of methyl 2-fluoro-4-cyanophenylacetate, 0.19 g of water was added, 1.15 grams of 95percent anhydrous calcium chloride and 15 grams of N, N-dimethylacetamide, stirring warming, 140 ~ 145 incubated for 20 to 24 hours (HPLC monitoring, the conversion rate> 99percent), The mixture was cooled to 60-70 ° C, concentrated under reduced pressure and purified by column chromatography to give 3-fluoro-4-methylbenzonitrile and 0.62 g of a pale yellow solid in a yield of 89.0percent.In a 1 L four-necked flask were placed 168.4 g of diethyl 2- (4-cyano-2-fluorophenyl) -1, 3-propanedioate (1 eq), 21.7 g of water140.9 grams of 95percent anhydrous calcium chloride (2eq) and 606 grams of N, N-dimethylacetamide, Stirring warming, 140 ~ 145 incubated for 20 to 24 hours, Cooling to 30 ° C, adding 352.5 grams of water, 303 grams of methylene chloride, adding about 70.2 grams of concentrated hydrochloric acid, To the system pH = 5 ~ 7, the liquid separation, the aqueous layer was extracted with dichloromethane, the organic phase was combined and the organic phase was concentrated under reduced pressure to give DMAc concentrated solution of 3-fluoro-4-methylbenzonitrile, The vacuum distillation was continued and 3-fluoro-4-methylbenzonitrile was collected until no product was distilled off to give 58.0 g of a white solid in a yield of 71.2percent.To a 20 L reactor was added 3400 g of compound B, compound C 8190 g, 7051 g of potassium carbonate, 175 g of phase transfer catalyst (tetrabutylammonium bromide), N, N-dimethylformamide 11L, nitrogen protection, stirring, heating to 100 C, The temperature is controlled at 100±5 C., the reaction is completed, the mixture is filtered, the cake is beaten, the filtrate is concentrated, washed with water, and desolvated to obtain an oily mixture D 6420 g, which is put into the next reaction.200 g of the crude product of the mixed compound D obtained in the previous step was added to 400 mL of dimethyl sulfoxide, and 167.9 g of sodium chloride solid was added thereto, and the mixture was stirred under nitrogen, and the temperature was raised to 160 C.25.8g of water was added dropwise, and the speed of the dripping water was controlled according to the index of temperature control between 160±5C, and the partially refluxed solvent was separated. The reaction was completed.300 mL of water was added dropwise for steam distillation, and the oil layer was collected.Add 50 mL of n-heptane, stir to dissolve completely, and cool down to 0-3 C to crystallize.Filter and dry to obtain pure product A 50g.In the first step, the second step and the total purification yield are about 48%, and the content is 99.7%.

Molecular Weight:135.14
XLogP3:2.1
Hydrogen Bond Acceptor Count:2
Exact Mass:135.048427358
Monoisotopic Mass:135.048427358
Topological Polar Surface Area:23.8
Heavy Atom Count:10
Complexity:158
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes