methyl 4-bromo-3-hydroxybenzoate

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:0.00; pressure:0.00; stir:

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

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

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of methyl 4-bromo-3-hydroxybenzoate (2.5 g) in acetonitrile (0.5 mL) and DMF (10 mL) in a microwave tube was added potassium carbonate (2.93 g) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (2.79 g). The mixture was heated to 150° C. in a microwave oven for 30 minutes. The solvent was removed in vacuum, ethyl acetate was added and the mixture was washed with water. The organic phase was washed with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum. Recrystallization of the residue from ethanol gave 1.2 g of the title compound. The mother liquor was concentrated in vacuum and purified by aminophase-silica-gel chromatography followed by recrystallized from methanol and water to give further 0.64 g of the title compound. The solvent was removed in vacuum, ethyl acetate was added the mixture was washed with water The organic phase was washed with saturated sodium chloride solution dried (sodium sulfate) the solvent was removed in vacuum Recrystallization of the residue from ethanol

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

Procedure: To a stirred solution of methyl 4-bromo-3-hydroxybenzoate (10.0 g) in DMF (50 mL) was added potassium carbonate (17.9 g) and iodomethane (9.2 mg). The mixture was stirred at room temperature for 2 h. Ethyl acetate was added and the mixture was washed with water. The organic phase was washed with saturated sodium chloride solution, dried (sodium sulfate) and the solvent was removed in vacuum to give 10 g of the title compound, that was used without further purification. the mixture was washed with water The organic phase was washed with saturated sodium chloride solution dried (sodium sulfate) the solvent was removed in vacuum

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

Procedure: 1.6 g of triphenylphosphine and 1 g of 4-Bromo-3-hydroxy-benzoic acid methyl ester were dissolved in 15 ml of anhydrous THF. The solution was cooled to 0° C. to 10° C. and a solution of 0.88 ml DEAD in 5 ml anhydrous THF was added dropwise over 20 min. The reaction was warmed to RT and stirred for 45 min. A solution of 0.69 ml 2-(2,4-Dichlorophenyl)-ethanol in 2 ml anhydrous THF was added with cooling. The reaction was stirred at RT for 3 h, then the solvents were removed under reduced pressure. The residue was treated with n-heptane:ethyl acetate/1:1. The filtrate was dried under reduced pressure. The product was purified by silica gel chromatography, eluting with n-heptane:ethyl acetate/4:1 to n-heptane:ethyl acetate/1:1. Yield 2 g. The solution was cooled to 0° C. to 10° C. with cooling The reaction was stirred at RT for 3 h the solvents were removed under reduced pressure The residue was treated with n-heptane The filtrate was dried under reduced pressure The product was purified by silica gel chromatography eluting with n-heptane

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

Procedure: 1.6 g of triphenylphosphine and 1 g of 4-Bromo-3-hydroxy-benzoic acid methyl ester were dissolved in 15 ml of anhydrous THF. The solution was cooled to 0° C. to 10° C. and a solution of 0.88 ml DEAD in 5 ml anhydrous THF was added dropwise over 20 min. The reaction was warmed to RT and stirred for 45 min. A solution of 0.69 ml 2-(2,4-Dichlorophenyl)-ethanol in 2 ml anhydrous THF was added with cooling. The reaction was stirred at RT for 3 h, then the solvents were removed under reduced pressure. The residue was treated with n-heptane:ethyl acetate/1:1. The filtrate was dried under reduced pressure. The product was purified by silica gel chromatography, eluting with n-heptane:ethyl acetate/4:1 to n-heptane:ethyl acetate/1:1. Yield 2 g. The solution was cooled to 0° C. to 10° C. with cooling The reaction was stirred at RT for 3 h the solvents were removed under reduced pressure The residue was treated with n-heptane The filtrate was dried under reduced pressure The product was purified by silica gel chromatography eluting with n-heptane

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.5 ml of thionyl chloride was added to 40 ml of MeOH at 0° C. The solution was stirred for 10 min and 5 g of 4-Bromo-3-hydroxy-benzoic acid was added. The reaction was stirred for 16 h at RT then heated to 50° C. for 3 h. The solvents were removed under reduced pressure. The residue was used directly in the next step. Yield 5.92 g The reaction was stirred for 16 h at RT The solvents were removed under reduced pressure