4-BROMODIBENZOFURAN

White Crysstalline

33.6 mg (200 mmol) of dibenzofuran was dissolved in 700 ml of THF under a nitrogen atmosphere. To this was added 350 ml of n-butyl lithium (1.6 mol/1 hexane solution) at −70° C. or less. After completion of addition, the mixture was stirred at −70° C or less for 1 hour. Then, the reaction mixture was heated to 0° C. and it was stirred for 1 hour. The reaction mixture was cooled again to −70° C. or less, and 45 g (300 ml) of 1, 2-dibromoethane was added dropwise. After completion of drop, the reaction mixture was stirred for 12 hours. Then, water was added to the reaction mixture, and the reaction product was extracted with ethyl acetate. The organic layer was washed with water, and the solvent was removed under a reduced pressure. The produced residue was recrystallized with hexane to obtain 37.1 g of an intermediate 1. The yield was 75percent. The structure of the compound was confirmed with NMR and mass spectrum.Synthesis of Intermediate 20 (0137) (0138) Under a nitrogen atmosphere, dibenzofuran (1.68 g, 10 mmol) was dissolved in tetrahydrofuran (10 mL), and mixed with n-BuLi (2.5 M, 4 mL) at −40° C. The cooling device was removed, and the reaction solution was placed in a water bath and warmed to room temperature in about 30 min, and then stirred for 2 hrs. Then, the reaction solution was cooled to −78° C., and 1, 2-dibromoethane (2.82 g, 15 mmol) in tetrahydrofuran (10 mL) was added dropwise. The cooling device was removed, and the mixture was placed in a water bath and warmed to room temperature in about 30 min, and then stood for 2 hrs. (0139) After the reaction was terminated, the reaction solution was washed with a saturated sodium chloride solution, taken up in a 2 N aqueous HCl solution, stirred for 30 min, and extracted with diethyl ether. (0140) The organic layer was dried over anhydrous magnesium sulfate to remove a small amount of water contained therein, suctioned, and concentrated. The resultant compound was purified by column chromatography eluting with Hex:EA=5:1, to obtain Intermediate 20 (1.83 g, 74percent). (0141) Intermediate 20 MS(FAB): 247(MUnder a nitrogen atmosphere, dibenzofuran (1.68 g, 10 mmol) was dissolved in tetrahydrofuran (10 mL), and mixed with n-BuLi (2.5 M, 4 mL) at −40° C. The cooling device was removed, and the reaction solution was placed in a water bath and warmed to room temperature in about 30 min, and then stirred for 2 hrs. Then, the reaction solution was cooled to −78° C., and 1, 2-dibromoethane (2.82 g, 15 mmol) in tetrahydrofuran (10 mL) was added dropwise. The cooling device was removed, and the mixture was placed in a water bath and warmed to room temperature in about 30 min, and then stood for 2 hrs.After the reaction was terminated, the reaction solution was washed with a saturated sodium chloride solution, taken up in a 2 N aqueous HCl solution, stirred for 30 min, and extracted with diethyl ether.The organic layer was dried over anhydrous magnesium sulfate to remove a small amount of water contained therein, suctioned, and concentrated. The resultant compound was purified by column chromatography eluting with Hex:EA=5:1, to obtain Intermediate 16 (1.83 g, 74percent).Intermediate 16 MS(FAB): 247(MIn an argon atmosphere, 600 ml of dehydrated tetrahydrofuran was added to 78.0 g (0.46 mol) of dibenzofuran. The resultant mixture was cooled to -30 °C and added with 300 ml (0.50 mol) of a 1.65 M hexane solution of n-butyllithium dropwise, and then, the temperature was raised to room temperature over one hour under stirring. After further stirring at room temperature for 5 h, the mixture was cooled to -60 °C and added with 60 ml (0.70 mol) of 1, 2-dibromoethane dropwise over one hour. [0166] After further stirring at room temperature for 15 h, the mixture was poured into 1000 ml of iced water and then extracted with dichloromethane. The organic layer was washed with a saturated saline solution, dried over MgSO[0182] In an argon atmosphere, 78.0 g (0.46 mol) of dibenzofuran was added with 600 ml of dehydrated tetrahydrofuran.The resultant mixture was cooled to -30 °C and added dropwise with 300 ml (0.50 mol) of a 1.65 M hexane solution ofn-butyllithium. The temperature was raised to room temperature over one hour under stirring. The mixture was stirredat room temperature for 5 h, cooled to - 60 °C, and then added dropwise with 60 ml (0.70 mol) of 1, 2-dibromoethaneover one hour.[0183] After stirring at room temperature for 15 h, the mixture was poured into 1000 ml of iced water and extractedwith dichloromethane. The organic layer was washed with brine, dried over MgSO4, filtered, and then concentrated. Theconcentrate was purified by silica gel column chromatography and washed with tetrahydrofuran/methanol to obtain 70g of solid, which was identified as the following intermediate 1-3 by FD-MS (yield: 62percent).Under an argon atmosphere, 600 mL of dehydrated tetrahydrofuran was added to 78.0 g of dibenzofuran and the mixture was cooled to −30° C. 300 mL of n-butyllithiumhexane solution (1.65 M) was then dropped and the mixture was heated to a room temperature over 1 hour under stirring. After being stirred for 5 hours at a room temperature, the mixture was cooled to −60° C., and 60 mL of 1, 2-dibromoethane was dropped thereto over 1 hour.After being stirred for 15 hours at a room temperature, the mixture was poured into 1000 mL of ice water, and the organic phase was extracted with dichloromethane. The extracted organic phase was washed with saturated saline, dried with anhydrous magnesium sulfate, and subjected to filtration and concentration. The solids obtained were purified with silica gel chromatography (with toluene), washed with tetrahydrofuran/methanol, and dried under reduced pressure to obtain 70 g of solids. The solids were identified as Intermediate 5 by FD-MS analysis.The starting material, 3-bromo- [1, 1'-biphenyl] -2-ol (32.42 g, 130.15 mmol)To a round bottom flask was added Pd (OAc) 2 (2.92 g, 13.01 mmol), 3-nitropyridine (1.62 g, 13.01 mmol) andAdd together C6F6 (195ml), After dissolving in DMI (130 ml)Tert-butyl peroxybenzoate (50.56 g, 260.30 mmol)And the mixture was stirred at 90 ° C.After the reaction was completed, the reaction mixture was extracted with CH2Cl2 and water. The organic layer was dried over MgSO4 and concentrated. The resulting compound was purified by silicagel column and recrystallized to obtain 15.76 g (yield: 49percent) of the product3-bromo-[1, 1’-biphenyl]-2-ol (32.42 g, 130.15 mmol) as a starting material, Pd(OAc)2 (2.92 g, 13.01 mmol), and 3-nitropyridine (1.62 g, 13.01 mmol) were added into a round bottom flask, then, dissolved in C5F5 (195 ml), DM1 (130 ml). After adding tert-butyl peroxybenzoate (50.56 g, 260.30 mmol), stirring at 90 D was followed. When the reaction was completed, the reaction product was extracted with CH2C12 and water, and then, the organic layer was dried with Mg504 and concentrated. Then, the concen-continued trate was passed through silica gel colunm, then recrystallized to obtain 15.76 g (yield: 49percent) of the product.

Molecular Weight:247.09
XLogP3:4.8
Hydrogen Bond Acceptor Count:1
Exact Mass:245.96803
Monoisotopic Mass:245.96803
Topological Polar Surface Area:13.1
Heavy Atom Count:14
Complexity:218
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes