* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
To a solution of 6-bromo-4-chloro-quinoline (12.12 g, 50 mmol) in methanol (200 mL) was added sodium methoxide (13.50 g, 250 mmol) at room temperature. Then, the reaction mixture was heated to 120 C. for 15 h in a sealed reaction flask. After cooling to room temperature, the methanol was removed under the vacuum and the residue was diluted with water. Then, the solids were collected by filtration and washed with water. After drying in air, 10.8 g (90.8% yield) of 6-bromo-4-methoxy-quinoline was isolated as a white solid which can be crystallized from acetonitrile: EI-HRMS m/e calcd for C10H8BrNO (M+) 236.9789, found 236.9784.
36%
In methanol; at 120℃; for 1h;Microwave irradiation;
300 mg (1.24 mmol) of 6-bromo-4-chloroquinoline [Lin et al., J. Med. Chem. 1978, 21, 268] was taken up in 4 ml methanol and 1.15 ml (6.19 mmol) methanolic sodium methylate solution (30 wt.%) was added. Then it was reacted in a single mode microwave for 1 h at 1200C. The solvent was removed in a rotary evaporator and the residue was partitioned between water and ethyl acetate. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over magnesium sulfate. The solvent was removed by distillation at reduced pressure. In this way we obtained 150 mg (36% of theor.) of the target compound.LC-MS (method 2): R, = 1.24 min; MS (EIpos): m/z = 238 [M]+.
With potassium acetate;dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; In 1,4-dioxane; at 110℃;Inert atmosphere;
Under an argon atmosphere, 150 mg of example 87A was dissolved in 4 ml dioxane. Then 111.3 mg (1.134 mmol) potassium acetate, 41.2 mg (0.050 mmol) of 1, l'-bis-(diphenylphosphino)- ferrocene palladium(II) chloride-dichloromethane complex and 176 mg (0.693 mmol) of 4,4,4'4'5,5,5'5'-octamethyl-2,2'-bi-l,3,2-dioxaborolan were added. The reaction mixture was stirred overnight at 1100C oil bath temperature. After cooling, dichloromethane was added to the reaction mixture and it was filtered on kieselguhr. It was washed again with ethyl acetate. The filtrate was concentrated in a rotary evaporator at reduced pressure and dried under high vacuum. We obtained 227 mg of 4-methoxy-6-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)quinoline [47%, (LC-MS)] as raw product. This was reacted subsequently without further purification.
To a solution of <strong>[874792-20-8]6-bromo-4-methoxy-quinoline</strong> (8.91 g, 37.42 mmol) in THF (tetrahydrofuran) (155 mL) was added dropwise a 2.5M solution of n-butyllithium in hexanes (16.46 mL, 4.16 mmol, 1.1 equiv.) at -70 C. During the addition, the temperature of the reaction mixture was raised slightly to -60 C. and it gave a very dark brown solution. The resulting colored solution was stirred for 30 min at this temperature. Then, a solution of dimethylformamide (5.78 mL, 74.84 mmol) in THF (10 mL) was added dropwise. After addition, the mixture was allowed to warm to room temperature and stirred for 15 h. Then, the mixture was diluted with saturated ammonium chloride solution and the two layers were separated. The aqueous layer was extracted with ethyl acetate (3*1 50 mL). The combined organic extracts were washed with brine solution and dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent under the vacuum gave the crude brown solid. This solid was dissolved in acetonitrile (~50 mL) at hot condition and then stored in the refrigerator overnight. The solids were collected by filtration and washed with diethyl ether. After drying in air, 4.47 g (64% yield) of 4-methoxy-quinoline-6-carbaldehyde was isolated as a white solid: EI-HRMS m/e calcd for C11H9NO2 (M+) 187.0633, found 187.0638.
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