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15 g of 2-isopropyl-N-phenylaniline obtained in Preparation Example 3 was placed in a round bottom three-necked flask,Concentrated sulfuric acid was added dropwise at room temperature and the mixture was stirred.After completion of the dropwise addition,The mixture was further stirred at room temperature for 5 hours. then,The organic layer was washed with ethyl acetate and water, extracted, concentrated and separated by column,9,9-dimethyl-9,10-dihydroacridine (13.4 g, 90percent yield) was obtained.
With dicyclohexyl(2-methoxy-6-methylbiphenyl-2<SUP>,</SUP>-yl)phosphine; potassium <i>tert</i>-butylate; palladium diacetate In 1,4-dioxane at 160℃; for 0.166667h; Inert atmosphere; Microwave irradiation;
79%
With sodium t-butanolate In toluene at 100℃; for 24h;
73%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium t-butanolate In toluene at 100℃; for 16h; Inert atmosphere;
With C22H26Cl2NPPd; sodium t-butanolate In toluene at 110℃; for 22h; Inert atmosphere;
4.2.1 Aryl amination general procedures
General procedure: Under a nitrogen atmosphere, an 8-mL vial was charged with NaOtBu (135 mg, 1.40 mmol), toluene (2 mL), aryl halide (1.0 mmol), amine (1.2 mmol) and (3IP)PdCl2 (5.6 mg, 11 μmol, 1.1 mol%). For the lower boiling amines (as noted in the data tables), 8 mL of toluene was used in order to minimize headspace within the vial. The reaction mixture was stirred and heated at 110 °C for 22 h. An aliquot of the resulting mixture was diluted with diethyl ether (1.8 mL), filtered through an alumina column and analyzed by gas chromatography. Bulk products were then isolated via column chromatography (silica; 10% ethyl acetate in pentane, unless otherwise noted) and further characterized by 1H and 13C NMR spectroscopy, as well as high-resolution mass spectrometry.
In tetrahydrofuran; at 0 - 20℃; for 5h;Inert atmosphere;
The above-obtained 20 g of methyl-2- (phenylamino) benzoate was placed in a round bottom three-necked flask under a nitrogen atmosphere,300 ml of THF was added,The mixture was dissolved by stirring,And cooling the solution to 0 C.Samples of CH3MgBr dissolved in THF were slowly added dropwise.After the completion of the drop,The mixture was slowly warmed to room temperature,And stirred for 5 hours.then,The organic layer was washed with ethyl acetate and water. The organic layer was extracted and concentrated and separated by column,Thereby obtaining 2-isopropyl-N-phenylaniline (16.9 g, 91% yield).
With palladium diacetate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; sodium t-butanolate; In toluene; at 110℃;
26.9 g Intermediate (22) and 37.8 g 4,6-dibromo dibenzofuran were added into a dry 2 L three-neck flask, followed by adding 800 mL dry and degassed toluene to dissolve. Then, 33.4 g sodium tert-butoxide (3.0 eq.), 0.52 g catalyst palladium diacetate (2% mol) and 2.9 g 1,1?-binaphthyl-2,2?-bis(diphenylphosphino) (BINAP, 4% mol) ligand were added. The reaction mixture was heated up to 110 C. and reacted overnight. After the reaction finished and the reaction mixture was cooled down to room temperature. The residual was absorbed by the added activated carbon, filtered by suction filtration and removed with solvent by rotary evaporation, followed by recrystallization with a mixture of toluene and ethanol, to produce 47.6 g Intermediate (23) at a yield of 90%.