1-(4-Fluorophenyl)-1-butanone

In a 500ml 4-neck flask, n-butyryl chloride (55. 5g, 0. 52mol) was dissolved in dichloroethane (250ml), were stirredUniform, cooled to about billion ° C, the fluorobenzene (52. 1, 0. 57mol) was dissolved in 100ml of dichloroethane was added dropwise n-butyl chloride solution, drip complete, heat the reaction, TLC or the reaction was monitored by gas chromatography , after the completion of the reaction, the solution was poured into dilute hydrochloric acid and ice, stirred LH, allowed to stand, the organic phase was separated, washed with water, washed with saturated sodium carbonate solution, removing solvent, distillation under reduced pressure to give the final product 77. 8g(Condition collected fractions: 102 ~105 ° C / 9mm Hg), yield 90percent, purity 99.0percentTo a solution of anhydrous A1C13 (13.8 g, 104 mmol) in DCM (10 mL) at 0C was added solution of butyryl chloride (7.0 mL, 78.1 mmol) in DCM (25 mL) and the reaction mixture was stirred at RT for 1H. To this a solution of fluorobenzene (CV, 5.0 g, 52.0 mmol) in DCM (15 mL) was added drop wise and the reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched with water and extracted with EtOAc. The combined organic layer was washed with brine, dried over anhydrous Na2S04 and concentrated under reduced pressure. The crude product was purified by column chromatography using 5percent EtOAc/hexane to afford compound DA (3.5 g, 40.6 percent) as an off white solid LC-MS: m/z 167.01 [M+H]+.EXAMPLE 10 In a 500ml 4-neck flask, n-butyryl chloride (55. 5g, 0. 52mol) was dissolved in dichloroethane (250ml), were stirredUniform, cooled to about billion C, the fluorobenzene (52. 1, 0. 57mol) was dissolved in 100ml of dichloroethane was added dropwise n-butyl chloride solution, drip complete, heat the reaction, TLC or the reaction was monitored by gas chromatography , after the completion of the reaction, the solution was poured into dilute hydrochloric acid and ice, stirred LH, allowed to stand, the organic phase was separated, washed with water, washed with saturated sodium carbonate solution, removing solvent, distillation under reduced pressure to give the final product 77. 8g(Condition collected fractions: 102 ~105 C / 9mm Hg), yield 90%, purity 99.0%To a solution of anhydrous A1C13 (13.8 g, 104 mmol) in DCM (10 mL) at 0C was added solution of butyryl chloride (7.0 mL, 78.1 mmol) in DCM (25 mL) and the reaction mixture was stirred at RT for 1H. To this a solution of fluorobenzene (CV, 5.0 g, 52.0 mmol) in DCM (15 mL) was added drop wise and the reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was quenched with water and extracted with EtOAc. The combined organic layer was washed with brine, dried over anhydrous Na2S04 and concentrated under reduced pressure. The crude product was purified by column chromatography using 5% EtOAc/hexane to afford compound DA (3.5 g, 40.6 %) as an off white solid LC-MS: m/z 167.01 [M+H]+.In a 500 mL four-necked flask equipped with a mechanical stirrer, a thermometer, a constant pressure dropping funnel and a ball reflux condenser58.1 g (0.44 mol) of anhydrous aluminum trichloride, 34.9 g (0.36 mol) of fluorobenzene and 90 mL1, 2-dichloroethane at 10 C46.5 g (0.44 mol) of n-butyryl chloride are slowly added below, and the mixture is stirred for 4 to 6 h at 35 to 45 C. Allow the reaction to cool to room temperatureThe mixture was poured into hydrochloric acid-ice water and stirred for 30 min. The layers were separated, the organic phase was separated and the organic phase was washed with sodium hydroxide solution (exceptTo the system of n-butyric acid), and then washed the organic phase once, desolventizing, solvent recovery, to give 500 ml of fluorobenzene and 1.0 mol of aluminum trichloride were added to the three-necked flask, and the temperature was lowered to 0 C. 1 mol of n-butyryl chloride was slowly added dropwise, and the dropping rate was 1.5 mL/min. After the completion of the dropwise addition, the reaction was kept for 3 hours, and then the temperature was raised to After incubation at 25 C for 30 hours, after the GC reaction is completed, hydrolysis is carried out. When the hydrolysis is carried out, the reaction solution is slowly poured into 300 ml of 10% diluted hydrochloric acid ice water mixture.In the middle, keep the hydrolysis temperature not more than 60 C, stir for 30 min, then let stand for 60 min to separate the layers, take the oil phase and wash it twice with 200 ml of water, stir for 30 min, and let stand for 60 min to separate the oil phase (the oil phase Contains compound I-2) into the next stepoperating.a) Preparation of 4' fluorobutyrophenone Aluminum chloride (139 g, 1.04 mol) was added to a solution of butyryl chloride (55.45 g, 0.520 mol, Aldrich) in dichloromethane (500 ml) stirring under a nitrogen atmosphere at 25 C. A solution of fluorobenzene (50.1 g, 0.521 mol, Aldrich) in dichloromethane was added and stirring was continued for 18 h. The reaction solution was poured over ice and extracted with dichloromethane (3*400 ml). The combined dichloromethane extractions were washed with deionized water (2*250 ml), 1.0N hydrochloric acid (500 ml), saturated sodium bicarbonate solution (2*500 ml) and deionized water (4*250 ml), concentrated by spin evaporation in vacuo. This material was combined with material from a similar preparation (using 0.26 mol of fluorobenzene) for distillation. Distillation at reduced pressure gave 69.27 g (53%) of a) Preparation of 4'fluorobutyrophenone Aluminum chloride (1.39 g, 1.04 mol) was added to a solution of butyryl chloride (55.45 g, 0.520 mol, Aldrich) in dichloromethane (500 ml) stirring under a nitrogen atmosphere at 25 C. A solution of fluorobenzene (50.1 g, 0.521 mol, Aldrich) in dichloromethane was added and stirring was continued for 18 h. The reaction solution was poured over ice and extracted with dichloromethane (3*400 ml). The combined dichloromethane extractions were washed with deionized water (2*250 ml), 1.0N hydrochloric acid (500 ml), saturated sodium bicarbonate solution (2*500 ml) and deionized water (4*250 ml), concentrated by spin evaporation in vacuo. This material was combined with material from a similar preparation (using 0.26 mol of fluorobenzene) for distillation. Distillation at reduced pressure gave 69.27 g (53%) of

Molecular Weight:166.19
XLogP3:2.5
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:3
Exact Mass:166.079393132
Monoisotopic Mass:166.079393132
Topological Polar Surface Area:17.1
Heavy Atom Count:12
Complexity:148
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes