methyl 5-bromo-2-iodobenzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred slurry of methyl 2-iodo-benzoate (5.0 g, 0.019 mol) and N-bromosuccinimide (3.74 g, 0.021 mol) in acetic acid (10 mL) was added concentrated H2SO4 (10 mL) dropwise, keeping the temperature at 20-40° C. The mixture was stirred at room temperature for 88 hours and then heated at 50° C. for 4 hours. The mixture was cooled to 10° C., treated with 40 g of ice water, and extracted with 50 mL of CH2Cl2. The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water, and concentrated to colorless oil. The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane) to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 7.92 (d, J=4 Hz, 1H), 7.83 (d, J=8 Hz, 1H), 7.27 (dd, J=8, 4 Hz, 1H), 3.92 (s, 3H); MS (DCl/NH3) [M+NH4]+ at 358, [M+NH3NH4]+ at 375. at 20-40° C heated at 50° C. for 4 hours The mixture was cooled to 10° C. extracted with 50 mL of CH2Cl2 The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water concentrated to colorless oil The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred slurry of methyl 2-iodo-benzoate (5.0 g, 0.019 mol) and N-bromosuccinimide (3.74 g, 0.021 mol) in acetic acid (10 mL) was added concentrated H2SO4 (10 mL) dropwise, keeping the temperature at 20-40° C. The mixture was stirred at room temperature for 88 hours and then heated at 50° C. for 4 hours. The mixture was cooled to 10° C., treated with 40 g of ice water, and extracted with 50 mL of CH2Cl2. The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water, and concentrated to colorless oil. The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane) to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 7.92 (d, J=4 Hz, 1H), 7.83 (d, J=8 Hz, 1H), 7.27 (dd, J=8, 4 Hz, 1H), 3.92 (s, 3H); MS (DCl/NH3) [M+NH4]+ at 358, [M+NH3NH4]+ at 375. at 20-40° C heated at 50° C. for 4 hours The mixture was cooled to 10° C. extracted with 50 mL of CH2Cl2 The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water concentrated to colorless oil The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred slurry of methyl 2-iodo-benzoate (5.0 g, 0.019 mol) and N-bromosuccinimide (3.74 g, 0.021 mol) in acetic acid (10 mL) was added concentrated H2SO4 (10 mL) dropwise, keeping the temperature at 20–40° C. The mixture was stirred at room temperature for 88 hours and then heated at 50° C. for 4 hours. The mixture was cooled to 10° C., treated with 40 g of ice water, and extracted with 50 mL of CH2Cl2. The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water, and concentrated to colorless oil. The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane) to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 7.92 (d, J=4 Hz, 1H), 7.83 (d, J=8 Hz, 1H), 7.27 (dd, J=8, 4 Hz, 1H), 3.92 (s, 3H); MS (DCI/NH3) [M+NH4]+ at 358, [M+NH3—NH4]+ at 375. at 20–40° C heated at 50° C. for 4 hours The mixture was cooled to 10° C. extracted with 50 mL of CH2Cl2 The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water concentrated to colorless oil The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred slurry of methyl 2-iodo-benzoate (5.0 g, 0.019 mol) and N-bromosuccinimide (3.74 g, 0.021 mol) in acetic acid (10 mL) was added concentrated H2SO4 (10 mL) dropwise, keeping the temperature at 20-40° C. The mixture was stirred at room temperature for 88 hours and then heated at 50° C. for 4 hours. The mixture was cooled to 10° C., treated with 40 g of ice water, and extracted with 50 mL of CH2Cl2. The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water, and concentrated to colorless oil. The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane) to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 7.92 (d, J=4 Hz, 1H), 7.83 (d, J=8 Hz, 1H), 7.27 (dd, J=8, 4 Hz, 1H), 3.92 (s, 3H); MS (DCl/NH3) [M+NH4]+ at 358, [M+NH3.NH4]+ at 375. at 20-40° C heated at 50° C. for 4 hours The mixture was cooled to 10° C. extracted with 50 mL of CH2Cl2 The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water concentrated to colorless oil The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred slurry of methyl 2-iodo-benzoate (5.0 g, 0.019 mol) and N-bromosuccinimide (3.74 g, 0.021 mol) in acetic acid (10 mL) was added concentrated H2SO4 (10 mL) dropwise, keeping the temperature at 20-40° C. The mixture was stirred at room temperature for 88 hours and then heated at 50° C. for 4 hours. The mixture was cooled to 10° C., treated with 40 g of ice water, and extracted with 50 mL of CH2Cl2. The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water, and concentrated to colorless oil. The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane) to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 7.92 (d, J=4 Hz, 1H), 7.83 (d, J=8 Hz, 1H), 7.27 (dd, J=8, 4 Hz, 1H), 3.92 (s, 3H); MS (DCl/NH3) [M+NH4]+ at 358, [M+NH3NH4]+ at 375. at 20-40° C heated at 50° C. for 4 hours The mixture was cooled to 10° C. extracted with 50 mL of CH2Cl2 The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water concentrated to colorless oil The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:

実験手順: To a solution of methyl 5-bromo-2-iodobenzoate (2.1 g, 6.16 mmol) in DME (15 mL) were morpholine (0.593 mL, 6.78 mmol), rac-2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (0.384 g, 0.62 mmol), Palladium acetate (0.138 g, 0.62 mmol) and CESIUM CARBONATE (2.81 g, 8.62 mmol) added. The mixture was heated in the microwave oven for 1h. The solvent was evaporated and the crude product was added to a silica gel column, 0-25% EtOAc in heptane yielding [Products]

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred slurry of methyl 2-iodo-benzoate (5.0 g, 0.019 mol) and N-bromosuccinimide (3.74 g, 0.021 mol) in acetic acid (10 mL) was added concentrated H2SO4 (10 mL) dropwise, keeping the temperature at 20-40° C. The mixture was stirred at room temperature for 88 hours and then heated at 50° C. for 4 hours. The mixture was cooled to 10° C., treated with 40 g of ice water, and extracted with 50 mL of CH2Cl2. The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water, and concentrated to colorless oil. The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane) to provide the title compound. 1H NMR (CDCl3, 400 MHz) δ 7.92 (d, J=4 Hz, 1H), 7.83 (d, J=8 Hz, 1H), 7.27 (dd, J=8, 4 Hz, 1H), 3.92 (s, 3H); MS (DCI/NH3) [M+NH4]+ at 358, [M+NH3NH4]+ at 375. at 20-40° C heated at 50° C. for 4 hours The mixture was cooled to 10° C. extracted with 50 mL of CH2Cl2 The organic phase was washed in succession with 2×50 mL 5% NaHCO3, 50 mL 10% Na2S2O3, 50 mL water concentrated to colorless oil The residue was purified by column chromatography (silica gel, 10:90 EtOAc:hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To methyl 5-bromo-2-iodobenzoate (4.41 g, 13 mmol), phenylboronic acid (1.6 g, 13 mmol), potassium carbonate (3.6 g, 26 mmol), and cesium carbonate (4.2 g, 13 mmol) in DMF (50 mL, sparged with nitrogen) was added palladium(0) tetrakis(triphenylphosphine) (751 mg, 0.65 mmol). The reaction was refluxed 16 h, cooled and washed with water, 1N hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (5% ethyl acetate/hexane) to yield methyl 4-bromo-1,1′-biphenyl-2-carboxylate (1.3 g). To methyl 4-bromo-1,1′-biphenyl-2-carboxylate (500 mg, 1.72 mmol) and Pd(dppf)Cl2—CH2Cl2 (70 mg, 0.086 mmol) in THF (5 mL) was added 1M neopentyl magnesium chloride (5 mL, 5 mmol) slowly at room temperature. The reaction was stirred overnight and then quenched with water. The reaction was diluted in ethyl acetate, and the resulting brown solid was filtered away. The organic layer was washed with water, 1N hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride. The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (1% ethyl acetate/hexane) to yield a yellow solid (200 mg). The reaction was refluxed 16 h cooled washed with water, 1N hydrochloric acid, saturated sodium bicarbonate, and saturated sodium chloride The organic layer was dried over sodium sulfate filtered concentrated under reduced pressure The residue was purified by flash chromatography (5% ethyl acetate/hexane)