ethyl 7-bromo-1-benzofuran-3-carboxylate

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

Procedure: To a solution of ethyl 7-bromo-1-benzofuran-3-carboxylate (1.0 g, 3.7 mmol) in 20 mL of MeOH/THF/H2O (2/211) was added LiOH H2O (777 mg, 18.5 mmol), and the mixture was stirred at ambient temperature overnight. The solvents were removed under vacuum, and the residue was added 10 mL of water and extracted with ether (100 mL). The aqueous layer was then acidified with 4 N HCl to pH=3 in ice bath, and extracted with EtOAc. The combined organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated to give 7-bromo-1-benzofuran-3-carboxylic acid. The solvents were removed under vacuum the residue was added 10 mL of water extracted with ether (100 mL) extracted with EtOAc The combined organic phase was washed with brine dried over anhydrous sodium sulfate concentrated

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

Procedure: A solution of 3-bromo-2-hydroxybenzaldehyde (20 g, 0.1 mol) in 150 mL of CH2Cl2 was added HBF4.Et2O (1.5 mL, 0.01 mmol). A solution of ethyl diazoacetate (27.36 g, 0.24 mol) in CH2Cl2 (50 mL) was introduced into the reaction mixture, during about 3-6 min and the evolution of N2 gas observed, and the reaction was not allowed to go above 38° C. Once gas evolution ceased, the reaction mixture was concentrated by rotary evaporator and H2SO4 (20 mL) was added to the mixture while stirring. After 30 min, the mixture was diluted with CH2Cl2 (200 mL) and the H2SO4 was quenched with solid NaHCO3. The mixture was then filtered through silica gel (100 g), and concentrated by rotary evaporator to give an oil, then exacted with EtOAc (500 mL), and washed with brine (100 mL), dried over Na2SO4. The solvent was concentrated in vacuo. The residue was separated and purified with silica gel chromatography to give product ethyl 7-bromo-1-benzofuran-3-carboxylate. to go above 38° C the reaction mixture was concentrated by rotary evaporator and H2SO4 (20 mL) was added to the mixture the mixture was diluted with CH2Cl2 (200 mL) the H2SO4 was quenched with solid NaHCO3 The mixture was then filtered through silica gel (100 g) concentrated by rotary evaporator to give an oil washed with brine (100 mL) dried over Na2SO4 The solvent was concentrated in vacuo The residue was separated purified with silica gel chromatography