| 76% |
With palladium diacetate; potassium carbonate; tris-(o-tolyl)phosphine; In toluene; at 60 - 120℃; for 25.5h;Inert atmosphere; |
In a 200 mL three-necked flask, 3.0 g (8.7 mmol) of<strong>[105404-89-5]3,6-dibromo-2,7-dimethoxynaphthalene</strong>,3.3 g (19 mmol) 4-chloro-2-fluorophenylboronic acid, 5.8 g (42 mmol) potassium carbonate, 0.13 g(0.43 mmol) of tris (2-methylphenyl) phosphine. To this mixture was added 85 mL of toluene.The mixture was degassed by stirring while reducing the pressure.To this mixture was added 19 mg (87 mumol) of palladium (II) acetateAnd the mixture was heated at 60 C. for 14 hours under a nitrogen stream,And the mixture was stirred at 120 C. for 11.5 hours. In addition, during the stirring,To the above mixture was added 3.0 g (17 mmol) of4-chloro-2-fluorophenylboronic acid,4.8 g (35 mmol) of potassium carbonate was added.After stirring, toluene was added to this mixture, suction filtration was carried out through Florisil (Wako Pure Chemical Industries, catalog number: 540-00135), Celite (Wako Pure Chemical Industries, catalog number: 531-16855), alumina, A filtrate was obtained, and the filtrate was concentrated to give an oil. The resulting oil was purified by silica gel column chromatography (developing solvent: toluene: heXanthene = 1: 2). The resulting solid was purified by high performance liquid column chromatography. High-performance liquid column chromatography was performed by using chloroform as a developing solvent. The obtained fraction was concentrated to obtain 5.8 g of a white solid of the objective compound in a yield of 76%. The synthesis scheme of Step 1 is shown below |
| 76% |
With palladium diacetate; potassium carbonate; tris-(o-tolyl)phosphine; In toluene; at 60 - 120℃; for 25.5h;Inert atmosphere; |
Into a 200-mL three-neck flask were put 3.0 g (8.7 mmol) of<strong>[105404-89-5]3,6-dibromo-2,7-dimethoxynaphthalene</strong>, 3.3 g (19 mmol) of 4-chloro-2-fluorophenylboronic15 acid, 5.8 g (42 mmol) of potassium carbonate, and 0.13 g (0.43 mmol) oftris(2-methylphenyl)phosphine. To this mixture was added 85 mL of toluene. The resultingmixture was degassed by being stirred while the pressure was reduced. To the mixture wasadded 19 mg (87 IJ.mol) of palladium(II) acetate, and stirring was performed under a nitrogenstream at 60 oc for 14 hours and then at 120 oc for 11.5 hours. In the midstream of the stirring,20 3.0 g (17 mmol) of 4-chloro-2-fluorophenylboronic acid and 4.8 g (35 mmol) of potassiumcarbonate were added to the resulting mixture.[0393]After the stirring, toluene was added to the mixture, and the resulting mixture wassuction-filtered through Florisil (manufactured by Wako Pure Chemical Industries, Ltd., Catalog25 No. 540-00135), Celite (manufactured by Wako Pure Chemical Industries, Ltd., Catalog No.531-16855), and alumina to give a filtrate. The filtrate was concentrated to give an oilysubstance. The obtained oily substance was purified by silica gel column chromatography (asthe developing solvent, toluene and hexane in a ratio of 1:2 were used). The resulting solid waspurified by high performance liquid column chromatography. The high performance liquid30 column chromatography was performed using chloroform as a developing solvent. Theobtained fractions were concentrated to obtain 5.8 g of a white solid which was an objective substance in a yield of 76 %. |
| 73% |
With tetrakis(triphenylphosphine) palladium(0); In 1,4-dioxane; for 4h;Reflux; |
0.125 mol [intermediate 1-1] at room temperature,43.4 g and (4-chloro-2-fluorophenyl) boronic acid 0.301 mol, 52.5 g and Ce2CO3 0.815 mol, 266 g and TTP (tetrakis(triphenylphosphine)palladium(0)) 8 mol% 11.6 g was added with 500 mL of 1,4-dioxane and refluxed. After 4 hours, the reaction was cooled to room temperature, 500 ml of H2O was added, and extracted with EA.After filtration, the obtained solid was recrystallized from EA (ethyl acetate) and Hx (normal hexane) to obtain 0.09 mol of [Intermediate 1-2] and 41.0 g (yield 73%). |
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