ethyl 2-(3-bromophenoxy)acetate

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

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl (3-bromophenoxy)acetate (488 mg) in DME (10 mL) was added 3-(hydroxymethyl)phenylboronic acid (429 mg), 1,1′-bis(diphenylphosphino)ferrocene-palladium (II) dichloride (77 mg) and 2M Na2CO3 aqueous solution (5 mL) at ambient temperature. The reaction mixture was stirred at 80° C. for 7 hours. The resulting mixture was cooled to ambient temperature and diluted with EtOAc. The mixture was washed successively with water and brine. The organic layer was dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was purified by silica gel column chromatography (chloroform:MeOH=100:0-97:3) to give ethyl {[3′-(hydroxymethyl)-3-biphenylyl]oxy}acetate. The resulting mixture was cooled to ambient temperature The mixture was washed successively with water and brine The organic layer was dried over anhydrous MgSO4 filtered evaporated in vacuo The residue was purified by silica gel column chromatography (chloroform:MeOH=100:0-97:3)

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

Procedure: 3-Bromophenol (2.84 g, 16.4 mmol) was dissolved in dimethylformamide (50 ml) in a dry 100 ml flask under nitrogen. Sodium hydride (0.7 g of a 60% suspension in mineral oil, washed with hexane, 16.7 mmol) was added in portions and the mixture was stirred for one hour at room temperature. Ethyl bromoacetate (1.85 ml, 16.7 mmol) was added drop-wise and the reaction was stirred overnight at room temperature. Approximately two-thirds of the solvent was removed under reduced pressure and the residue was mixed with water (150 ml) and extracted with methylene chloride (3×20 ml). The extracts were combined, washed with water (50 ml), saturated sodium chloride solution (50 ml), then dried (MgSO4). The solution was filtered and concentrated which gave 4.18 g (98%) of ethyl 3-bromophenyloxyacetate. Sodium hydride (0.7 g of a 60% suspension in mineral oil, washed with hexane, 16.7 mmol) was added in portions the reaction was stirred overnight at room temperature Approximately two-thirds of the solvent was removed under reduced pressure the residue was mixed with water (150 ml) extracted with methylene chloride (3×20 ml) washed with water (50 ml), saturated sodium chloride solution (50 ml) dried (MgSO4) The solution was filtered concentrated which

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

Procedure: 2.6 g of the resulting ether compound, 5.3 g of tri-n-butyl(3-thienyl)tin and 20 mg of tetrakis(triphenylphosphine)palladium were dissolved in 10 ml of xylene, and the mixture was refluxed for 5.5 hours. A 25% aqueous solution of potassium fluoride was added to the solution, and then the precipitate was removed by filtration. The organic layer separated was worked up in a customary manner, and the product was purified by silica gel column chromatography [hexane/ethyl acetate=20/1→15/1] to give 1.7 g of ethyl 3-(3thienyl)phenoxyacetate as a white powder. the mixture was refluxed for 5.5 hours the precipitate was removed by filtration The organic layer separated the product was purified by silica gel column chromatography [hexane/ethyl acetate=20/1→15/1]

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

Procedure: 0.5 g of 3-bromophenol and 0.33 ml of ethyl bromoacetate were dissolved in 4 ml of dimethylformamide, and 0.4 g of potassium carbonate was added. The mixture was stirred at 65°-70° C. for 3.5 hours. The solvent was evaporated, and the residue was worked up in a customary manner to give 0.6 g of ethyl 3-bromophenoxyacetate as a colorless oil. The solvent was evaporated

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an Ar atmosphere, 12 mL of toluene, 3 mL of methanol, and 3 mL of 2M aqueous sodium carbonate solution were added to 500 mg (1.93 mmol) of ethyl (3-bromophenoxy)acetate and 352 mg (2.32 mmol) of (2-methoxyphenyl)boronic acid, and the mixture was degassed. Further, 112 mg (0.097 mmol) of tetrakis(triphenylphosphine)palladium(0) was added thereto, and the mixture was heated under stirring at 80° C. for 6 hours. After the mixture was cooled to room temperature, ethyl acetate and water were added thereto to separate the mixture. The water layer was separated, and filtration was performed. Thereafter, acidification was performed with 1N hydrochloric acid, and extraction with ethyl acetate was performed. The organic layer was washed with saturated saline and dried over anhydride magnesium sulfate, followed by filtration and condensation, thereby giving 290 mg of [(2′-methoxybiphenyl-3-yl)oxy]acetic acid (yield: 58%). the mixture was degassed the mixture was heated After the mixture was cooled to room temperature to separate the mixture The water layer was separated filtration Thereafter, acidification was performed with 1N hydrochloric acid, and extraction with ethyl acetate The organic layer was washed with saturated saline dried over anhydride magnesium sulfate followed by filtration and condensation

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

Procedure: When the same reactions as in Referential Example 12 are carried out using 3-bromothiophenol or 3-bromoaniline instead of the starting 3-bromophenol, 3-(3-thienyl)phenylthioacetic acid and 3-(3-thienyl)phenylaminoacetic acid are obtained. are obtained

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

Procedure: 2.6 g of the resulting ether compound, 5.3 g of tri-n-butyl(3-thienyl)tin and 20 mg of tetrakis(triphenhylphosphine)paladium were dissolved in 10 ml of xylene, and the mixture was refluxed for 5.5 hours. A 25% aqueous solution of potassium fluoride was added to the solution, and then the precipitate was removed by filtration. The organic layer separated was worked up in a customary manner, and the product was purified by silica gel column chromatography [hexane/ethyl acetate=20/1→15/1] to give 1.7 g of ethyl 3-(3-thienyl)phenoxyacetate as a white powder. the mixture was refluxed for 5.5 hours the precipitate was removed by filtration The organic layer separated the product was purified by silica gel column chromatography [hexane/ethyl acetate=20/1→15/1]

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

Procedure: 0.5 g of 3-bromophenol and 0.33 ml of ethyl bromoacetate were dissolved in 4 ml of dimethylformamide, and 0.4 g of potassium carbonate was added. The mixture was stirred at 65°-70° C. for 3.5 hours. The solvent was evaporated, and the residue was worked up in a customary manner to give 0.6 g of ethyl 3-bromophenoxyacetate as a colorless oil. The solvent was evaporated

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