* 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.
Reference:
[1] Chemical Science, 2018, vol. 9, # 15, p. 3860 - 3865
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[ 64150-61-4 ]
[ 271-89-6 ]
[ 59214-70-9 ]
Yield
Reaction Conditions
Operation in experiment
56%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium tetrahydroborate; N,N,N,N,-tetramethylethylenediamine In tetrahydrofuran at 23℃; for 0.7 h; Inert atmosphere
General procedure: PdCl2(dppf), PdCl2(tbpf) and (A.caPhos)PdCl2. A mixture of the halogenated heterocycle (0.66 mmol) in anhydrous THF (13.2 mL) was degassed by bubbling argon for few minutes. Then, PdCl2(dppf) (27.0 mg, 0.033 mmol, 5.0 molpercent), TMEDA (0.130 g, 1.12 mmol, 1.7 equiv) and finally NaBH4 (42.4 mg, 1.12 mmol, 1.7 equiv) were introduced in sequence. The mixture was stirred at room temperature under argon for the proper time and then worked up as described above.
Reference:
[1] Journal of Molecular Catalysis A: Chemical, 2014, vol. 393, p. 191 - 209
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[ 59214-70-9 ]
Reference:
[1] Journal of Organic Chemistry, 1996, vol. 61, # 18, p. 6244 - 6251
With bromine; potassium acetate; In dichloromethane; at 20℃;
To a stirred DCM solution (200 mL) containing benzofuran (24 g, 203 mmol) and potassium acetate (40 g, 408 mmol) 64.9 g of bromine (406 mmol) was slowly added at 20 C. as a solution in DCM (100 mL). The reaction mixture was stirred overnight at RT, poured into sodium thiosulfate solution and extracted with DCM. The organic layer was dried over anhydrous MgSO4, and the solution was evaporated. CombiFlash chromatography (hexanes) gave 33.6 g of the target product in 60% isolated yield.
15.86 g (57%)
With bromine; potassium acetate; sodium hydrogensulfite; In chloroform;
EXAMPLE 32 N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]benzofuro[3,2-c]pyridine-3-carboxamide <strong>[271-89-6]Benzofuran</strong> (11.02 ml, 100 mmol) and potassium acetate (1.96 g, 200 mmol) are dissolved in CHCl3 (50 ml). Bromine (10.3 ml, 200 mmol) is dissolved in CHCl3 (20 ml) and added dropwise. Following addition, the reaction is heated at 50 C. for 5 h. The mixture is cooled to rt and quenched onto 5% sodium bisulfite solution (100 ml). The layers are allowed to separate, and the organic is washed with 5% NaHCO3 (1*100 ml), dried over Na2SO4, filtered, and concentrated to a green oil. The crude material is chromatographed over 1 kg slurry-packed silica eluding with 100% pentane. The appropriate fractions are combined and concentrated to give 15.86 g (57%) of 2,3-dibromobenzofuran as a pale oil. HRMS (EI) calcd for C8H4Br2O: 273.8630, found 273.8624.
15.86 g (57%)
With bromine; potassium acetate; sodium hydrogensulfite; In chloroform;
EXAMPLE 27 N-[(1S,2R,4R)-7-azabicyclo[2.2.1]hept-2-yl]benzofuran[3,2-c]pyridine-3-carboxamide dihydrochloride <strong>[271-89-6]Benzofuran</strong> (11.02 ml, 100 mmol) and potassium acetate (1.96 g, 200 mmol) are dissolved in CHCl3 (50 ml). Bromine (10.3 ml, 200 mmol) is dissolved in CHCl3 (20 ml) and added dropwise. Following addition, the reaction is heated at 50 C. for 5 h. The mixture is cooled to RT and quenched onto 5% sodium bisulfite solution (100 ml). The layers are allowed to separate, and the organic is washed with 5% NaHCO3 (1*100 ml), dried over Na2SO4, filtered, and concentrated to a green oil. The crude material is chromatographed over 1 kg slurry-packed silica eluding with 100% pentane. The appropriate fractions are combined and concentrated to give 15.86 g (57%) of 2,3-dibromobenzofuran as a pale oil. HRMS (EI) calcd for C8H4Br2O: 273.8630, found 273.8624 (M)+.
Stage #1: dibromobenzofuran With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h;
Stage #2: carbon dioxide In tetrahydrofuran; hexane at -78 - 20℃;
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; sodium tetrahydroborate; N,N,N,N,-tetramethylethylenediamine; In tetrahydrofuran; at 23℃; for 0.7h;Inert atmosphere;
General procedure: PdCl2(dppf), PdCl2(tbpf) and (A.caPhos)PdCl2. A mixture of the halogenated heterocycle (0.66 mmol) in anhydrous THF (13.2 mL) was degassed by bubbling argon for few minutes. Then, PdCl2(dppf) (27.0 mg, 0.033 mmol, 5.0 mol%), TMEDA (0.130 g, 1.12 mmol, 1.7 equiv) and finally NaBH4 (42.4 mg, 1.12 mmol, 1.7 equiv) were introduced in sequence. The mixture was stirred at room temperature under argon for the proper time and then worked up as described above.
With bromine; potassium acetate; acetic acid; at 90℃; for 12h;
To an oven-dried two-neck round-bottom flask was added 2-bromobenzofuran (20.3 mmol, 1 equiv, 4 g) in acetic acid (20 mL) followed by KOAc (22.3 mmol, 1.1 equiv, 2.19 g). To this, bromine (23.34 mmol, 1.15 equiv, 1.2 mL) in acetic acid (20 mL) was added slowly. The reaction mixture was stirred for 12 h at 90 . It was brought to rt and quenched with 5 % aq. NaHSO3solution and extracted with diethyl ether. The organic extract was washed with brine, dried over anhydrous MgSO4and concentrated. The crude mixture was subjected to silica gel column chromatography using hexane as eluent to afford 2,3-dibromobenzofuran 1.1 as colourless liquid (3.8 g, 68%).