Cyclohexanone, 4-(4-chlorophenyl)-

White Solid

2-(4-(4-chlorophenyl)-1-hydroxycyclohexyl)-3, 4-dihydronaphthalen-1-(2H)-one (12.0 g, 0.0.034 mol) was charged in a reactor equipped with overhead stirrer, reflux condenser and thermo-pocket. Toluene (200 mL) was added to suspend the material and p-toluene sulfonic acid (0.3 g, 2.5 mol percent) was added to the reaction mass which was then heated to 60 °C and stirred for 6 h. Progress of reaction was monitored on TLC. After completion of reaction, reaction mass was cooled to RT and solvent was evaporated under pressure to obtain residue. To the residue, was added ethyl acetate (150 mL) and washed with sat. NaHC0The crude product 2 (150 g, 0.46 mol) obtained in the previous step was dissolved in anhydrous THF (750 ml)Then joinBiphenyl boronic acid(394.4 g, 1.55 mol), PdCl2 (dppf) (7.5 g, 5percent), Et3N (156.5 g, 1.55 mol), The reaction system was replaced with nitrogen twice, The reaction was heated to reflux for 12 hours.TLC detection reaction is complete, Quenching the reaction with water, After filtering the reaction solution, The filtrate was extracted twice with dichloromethane, Each time 500mL, Combined organic phase, After drying with anhydrous sodium sulfate, Concentrated organic phase, To give 140 g of the intermediate. dissolving the intermediate into methanol (600 mL)Then, 200 mL of an aqueous solution of copper chloride (104.5 g, 0.78 mol) was added, Reflux reaction for 6 hours, TLC detection reaction is complete, Cooled to room temperature, Dichloromethane (500 ml * 2) was extracted twice, Combined organic phase, Add 600ml saturated salt washed, Dried over anhydrous sodium sulfate, Concentrated organic phase, To give the product 4- (4-chlorophenyl) cyclohexanone as compound 3 (32.3 g, 0.15 mol)The yield is about 32percent.Step 4 A solution of the ketal P (5.81 g, 23.06 mmol) in acetone (200 mL) was treated with p-toluenesulfonic acid monohydrate (876 mg) and heated at 60° C. overnight. Solvent was removed and the residue was taken up in EtOAc, washed with aqueous Na2CO3 solution, brine, dried and concentrated to give the crude product as a yellow oil (5.38 g, >100percent yield). Purification through flash chromatography (heaxane/EtOAc, 80/20-->60/40) provided 4-(4-chlorophenyl)cyclohexanone as a light yellow oil (4.54 g, 95percent yield). MS (EI) m/e 208 (M+), Calcd for C12H13C102, 208.The crude product Compound 3 (50.8 g, about 0.14 mol) obtained in the previous step was added to ethanol (200 mL), and then added with 10 wtpercent KOH (20 g, 0.36 mol) in water and refluxed for 6 hours.After completion of the reaction by TLC, the reaction mixture was cooled to room temperature, adjusted to weakly basic (pH about 7-8) by adding sodium bicarbonate and extracted twice with ethyl acetate (300 mL). The organic phases were combined, The organic phase was washed with saturated brine (400 ml) and dried over anhydrous sodium sulfate. The organic phase was concentrated.The crude product obtained is subjected to column chromatographyPurification afforded compound 4 (15.8 g, 0.08 mol).Yield about 54percent.The crude product 2 (150 g, 0.46 mol) obtained in the previous step was dissolved in anhydrous THF (750 ml)Then joinBiphenyl boronic acid(394.4 g, 1.55 mol), PdCl2 (dppf) (7.5 g, 5percent), Et3N (156.5 g, 1.55 mol), The reaction system was replaced with nitrogen twice, The reaction was heated to reflux for 12 hours.TLC detection reaction is complete, Quenching the reaction with water, After filtering the reaction solution, The filtrate was extracted twice with dichloromethane, Each time 500mL, Combined organic phase, After drying with anhydrous sodium sulfate, Concentrated organic phase, To give 140 g of the intermediate. dissolving the intermediate into methanol (600 mL)Then, 200 mL of an aqueous solution of copper chloride (104.5 g, 0.78 mol) was added, Reflux reaction for 6 hours, TLC detection reaction is complete, Cooled to room temperature, Dichloromethane (500 ml * 2) was extracted twice, Combined organic phase, Add 600ml saturated salt washed, Dried over anhydrous sodium sulfate, Concentrated organic phase, To give the product 4- (4-chlorophenyl) cyclohexanone as compound 3 (32.3 g, 0.15 mol)The yield is about 32percent.

Molecular Weight:208.68
XLogP3:2.8
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:208.0654927
Monoisotopic Mass:208.0654927
Topological Polar Surface Area:17.1
Heavy Atom Count:14
Complexity:196
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes