1-(2-bromo-3-hydroxyphenyl)ethanone

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(2-Bromo-3-hydroxy phenyl)ethanone (6.50 g, 30.2 mmol), which had been obtained in Reference example 1(1c), and copper (I) iodide (2.51 g, 13.2 mmol) were dissolved in acetonitrile (150 mL), followed by addition of a solution of difluoro(fluorosulfonyl)acetic acid (50.0 g, 281 mmol) dissolved in acetonitrile (50 mL) over 1 hour and 30 minutes under heating at 55° C. Upon the completion of the dropwise addition, the reaction solution was stirred at 55° C. for 3 hours, cooled to room temperature, added with water, and then extracted with ethyl acetate/hexane (2:1, V/V). The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (neutral silica gel, hexane:ethyl acetate, 100:0-75:25, V/V and basic silica gel, hexane:ethyl acetate, 100:0-50:50, V/V) to give the title compound as a colorless oily substance (1.53 g, yield 18%). Upon the completion of the dropwise addition cooled to room temperature extracted with ethyl acetate/hexane (2:1, V/V) The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure The residue was purified by silica gel chromatography (neutral silica gel, hexane:ethyl acetate, 100:0-75:25, V/V and basic silica gel, hexane:ethyl acetate, 100:0-50:50, V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under nitrogen atmosphere, 1-(2-bromo-3-hydroxy phenyl)ethanone (6.50 g, 30.2 mmol), which had been obtained in Reference example 1(1c), and potassium carbonate (8.36 g, 60.5 mmol) were dissolved in N,N-dimethyl formamide (60 mL), and stirred at room temperature for 10 minutes. Subsequently, ethyl iodide (3.14 mL, 39.3 mmol) was added to the mixture, which was then further stirred for 21 hours. Ethyl acetate/hexane (1:1, V/V) and water were added to the reaction solution for fractionation, and the aqueous layer was extracted with ethyl acetate/hexane (1:1, V/V). The organic layers were combined, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate, 100:0-85:15, V/V) to give the title compound as a colorless oily substance (4.89 g, yield 67%). was then further stirred for 21 hours the aqueous layer was extracted with ethyl acetate/hexane (1:1, V/V) washed with saturated brine dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure The residue was purified by silica gel chromatography (hexane:ethyl acetate, 100:0-85:15, V/V)

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 1-(2-bromo-3-methoxy phenyl)ethanone (30.5 g, 229 mmol) which had been obtained in Reference example 1(1b) was dissolved in methylene chloride (500 mL), and added dropwise with a 1.0 M solution of tribromo phosphine in dichloromethane (293 mL, 293 mmol) at −80° C. over 5 hours. Upon the completion of the dropwise addition, the mixture was stirred for 17 hours at −40° C. Subsequently, the reaction solution was cooled to −80° C. and added dropwise with methanol (500 mL). Upon the completion of the dropwise addition, the temperature was raised to −40° C. followed by stirring for 3 hours. The temperature of the reaction solution was raised to room temperature. The solvent was distilled off under reduced pressure until the solution turned green. After adding ethanol, the mixture was extracted with ethyl acetate/hexane (1:1, V/V). After neutralization with a saturated aqueous solution of sodium hydrogen carbonate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate, 100:0-55:45, V/V) to give the title compound as a colorless oily substance (13.5 g, yield 47%). Upon the completion of the dropwise addition Subsequently, the reaction solution was cooled to −80° C. Upon the completion of the dropwise addition the temperature was raised to −40° C. by stirring for 3 hours The temperature of the reaction solution was raised to room temperature The solvent was distilled off under reduced pressure until the solution After adding ethanol the mixture was extracted with ethyl acetate/hexane (1:1, V/V) After neutralization with a saturated aqueous solution of sodium hydrogen carbonate, the solvent was distilled off under reduced pressure The residue was purified by silica gel chromatography (hexane:ethyl acetate, 100:0-55:45, V/V)

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-(2-Bromo-3-hydroxy phenyl)ethanone (6.50 g, 30.2 mmol), which had been obtained in Reference example 3 (3c), and copper (I) iodide (2.51 g, 13.2 mmol) were dissolved in acetonitrile (150 mL), followed by addition of a solution of difluoro(fluorosulfonyl)acetic acid (50.0 g, 281 mmol) dissolved in acetonitrile (50 mL) over 1 hour and 30 minutes under heating at 55° C. Upon the completion of the dropwise addition, the reaction solution was stirred at 55° C. for 3 hours, cooled to room temperature, added with water, and then extracted with ethyl acetate/hexane (2:1, V/V). The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (neutral silica gel, hexane:ethyl acetate, 100:0-75:25, V/V and basic silica gel, hexane:ethyl acetate, 100:0-50:50, V/V) to give the title compound as a colorless oily substance (1.53 g, yield 18%). Upon the completion of the dropwise addition cooled to room temperature extracted with ethyl acetate/hexane (2:1, V/V) The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure The residue was purified by silica gel chromatography (neutral silica gel, hexane:ethyl acetate, 100:0-75:25, V/V and basic silica gel, hexane:ethyl acetate, 100:0-50:50, V/V)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 1-(2-bromo-3-hydroxy phenyl)ethanone (6.50 g, 30.2 mmol), which had been obtained in Reference example 3 (3c), and potassium carbonate (8.36 g, 60.5 mmol) were dissolved in N,N-dimethyl formamide (60 mL), and stirred at room temperature for 10 minutes. Subsequently, ethyl iodide (3.14 mL, 39.3 mmol) was added to the mixture, which was then further stirred for 21 hours. Ethyl acetate/hexane (1:1, V/V) and water were added to the reaction solution for fractionation, and the aqueous layer was extracted with ethyl acetate/hexane (1:1, V/V). The organic layers were combined, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate, 100:0-85:15, V/V) to give the title compound as a colorless oily substance (4.89 g, yield 67%). was then further stirred for 21 hours the aqueous layer was extracted with ethyl acetate/hexane (1:1, V/V) washed with saturated brine dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure The residue was purified by silica gel chromatography (hexane:ethyl acetate, 100:0-85:15, V/V)

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under a nitrogen atmosphere, 1-(2-bromo-3-methoxy phenyl)ethanone (30.5 g, 229 mmol) which had been obtained in Reference example 3 (3b) was dissolved in methylene chloride (500 mL), and added dropwise with a 1.0 M solution of tribromo phosphine in dichloromethane (293 mL, 293 mmol) at −80° C. over 5 hours. Upon the completion of the dropwise addition, the mixture was stirred for 17 hours at −40° C. Subsequently, the reaction solution was cooled to −80° C. and added dropwise with methanol (500 mL). Upon the completion of the dropwise addition, the temperature was raised to −40° C. followed by stirring for 3 hours. The temperature of the reaction solution was raised to room temperature. The solvent was distilled off under reduced pressure until the solution turned green. After adding ethanol, the mixture was extracted with ethyl acetate/hexane (1:1, V/V). After neutralization with a saturated aqueous solution of sodium hydrogen carbonate, the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate, 100:0-55:45, V/V) to give the title compound as a colorless oily substance (13.5 g, yield 47%). Upon the completion of the dropwise addition Subsequently, the reaction solution was cooled to −80° C. Upon the completion of the dropwise addition the temperature was raised to −40° C. by stirring for 3 hours The temperature of the reaction solution was raised to room temperature The solvent was distilled off under reduced pressure until the solution After adding ethanol the mixture was extracted with ethyl acetate/hexane (1:1, V/V) After neutralization with a saturated aqueous solution of sodium hydrogen carbonate, the solvent was distilled off under reduced pressure The residue was purified by silica gel chromatography (hexane:ethyl acetate, 100:0-55:45, V/V)