ethyl 5-fluoro-2-hydroxybenzoate

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-fluorosalicylic acid (50 g) in absolute ethanol (500 ml), concentrated sulfuric acid (10 ml) was cautiously added. The solution was heated at 90° C. for 72 hours. The solvent was removed in vacuo, and the viscous residue was made basic (final pH=9) by portionwise addition of saturated aqueous sodium bicarbonate. The solution was then extracted with three 200 ml portions of methylene chloride. The combined organic extracts were dried (anhydrous sodium sulfate) and concentrated in vacuo to afford the title compound (quantitative yield) as a viscous colorless oil. The solvent was removed in vacuo by portionwise addition of saturated aqueous sodium bicarbonate The solution was then extracted with three 200 ml portions of methylene chloride The combined organic extracts were dried (anhydrous sodium sulfate) concentrated in vacuo

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-fluorosalicylic acid (50 g) in absolute ethanol (500 ml), concentrated sulfuric acid (10 ml) was cautiously added. The solution was heated at 90° C. for 72 hours. The solvent was removed in vacuo, and the viscous residue was made basic (final pH=9) by portionwise addition of saturated aqueous sodium bicarbonate. The solution was then extracted with three 200 ml portions of methylene chloride. The combined organic extracts were dried (anhydrous sodium sulfate) and concentrated in vacuo to afford the title compound (quantitative yield) as a viscous colorless oil. The solvent was removed in vacuo by portionwise addition of saturated aqueous sodium bicarbonate The solution was then extracted with three 200 ml portions of methylene chloride The combined organic extracts were dried (anhydrous sodium sulfate) concentrated in vacuo

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 5-fluorosalicylate (191 mg), 4-chloro-6,7-dimethoxyquinoline (125 mg), and 4-dimethylaminopyridine (205 mg) were suspended in o-dichlorobenzene (1 ml), and the suspension was stirred at 120° C. overnight. The reaction solution was cooled to room temperature, and the solvent was removed by distillation under the reduced pressure. Water was then added to the residue, and the mixture was extracted with chloroform. The chloroform layer was washed with water and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-hexane to give the title compound (64 mg, yield 22%). The reaction solution was cooled to room temperature the solvent was removed by distillation under the reduced pressure Water was then added to the residue the mixture was extracted with chloroform The chloroform layer was washed with water was dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by column chromatography

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

Procedure: 5-Fluoro-2-hydroxybenzoic acid (344 mg), 1-ethyl-3-(3-dimethylaminopropylcarbodiimide hydrochloride (420 mg), 1-hydroxybenzotriazole hydrate (337 mg), and ethanol (2 ml) were dissolved in N,N-dimethylformamide to prepare a solution which was then stirred at room temperature overnight. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-hexane to give ethyl 5-fluorosalicylate (191 mg, yield 28%). to prepare a solution which the mixture was extracted with ethyl acetate The ethyl acetate layer was then washed with water was dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by column chromatography

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 5-fluorosalicylate (191 mg), 4-chloro-6,7-dimethoxyquinoline (125 mg), and 4-dimethylaminopyridine (205 mg) were suspended in o-dichlorobenzene (1 ml), and the suspension was stirred at 120° C. overnight. The reaction solution was cooled to room temperature, and the solvent was removed by distillation under the reduced pressure. Water was then added to the residue, and the mixture was extracted with chloroform. The chloroform layer was washed with water and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-hexane to give the title compound (64 mg, yield 22%). The reaction solution was cooled to room temperature the solvent was removed by distillation under the reduced pressure Water was then added to the residue the mixture was extracted with chloroform The chloroform layer was washed with water was dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by column chromatography

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

Procedure: 5-Fluoro-2-hydroxybenzoic acid (344 mg), 1-ethyl-3-(3-dimethylaminopropylcarbodiimide hydrochloride (420 mg), 1-hydroxybenzotriazole hydrate (337 mg), and ethanol (2 ml) were dissolved in N,N-dimethylformamide to prepare a solution which was then stirred at room temperature overnight. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-hexane to give ethyl 5-fluorosalicylate (191 mg, yield 28%). to prepare a solution which the mixture was extracted with ethyl acetate The ethyl acetate layer was then washed with water was dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by column chromatography

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-fluorosalicylic acid (50 g) in absolute ethanol (500 ml), concentrated sulfuric acid (10 ml) was cautiously added. The solution was heated at 90° C. for 72 hours. The solvent was removed in vacuo, and the viscous residue was made basic (final pH=9) by portionwise addition of saturated aqueous sodium bicarbonate. The solution was then extracted with three 200 ml portions of methylene chloride. The combined organic extracts were dried (anhydrous sodium sulfate) and concentrated in vacuo to afford the title compound (quantitative yield) as a viscous colorless oil. The solvent was removed in vacuo by portionwise addition of saturated aqueous sodium bicarbonate The solution was then extracted with three 200 ml portions of methylene chloride The combined organic extracts were dried (anhydrous sodium sulfate) concentrated in vacuo

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 5-fluorosalicylic acid (50 g) in absolute ethanol (500 ml), concentrated sulfuric acid (10 ml) was cautiously added. The solution was heated at 90° C. for 72 hours. The solvent was removed in vacuo, and the viscous residue was made basic (final pH=9) by portionwise addition of saturated aqueous sodium bicarbonate. The solution was then extracted with three 200 ml portions of methylene chloride. The combined organic extracts were dried (anhydrous sodium sulfate) and concentrated in vacuo to afford the title compound (quantitative yield) as a viscous colorless oil. The solvent was removed in vacuo by portionwise addition of saturated aqueous sodium bicarbonate The solution was then extracted with three 200 ml portions of methylene chloride The combined organic extracts were dried (anhydrous sodium sulfate) concentrated in vacuo

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Ethyl 5-fluorosalicylate (191 mg), 4-chloro-6,7-dimethoxyquinoline (125 mg), and 4-dimethylaminopyridine (205 mg) were suspended in o-dichlorobenzene (1 ml), and the suspension was stirred at 120° C. overnight. The reaction solution was cooled to room temperature, and the solvent was removed by distillation under the reduced pressure. Water was then added to the residue, and the mixture was extracted with chloroform. The chloroform layer was washed with water and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-hexane to give the title compound (64 mg, yield 22%). The reaction solution was cooled to room temperature the solvent was removed by distillation under the reduced pressure Water was then added to the residue the mixture was extracted with chloroform The chloroform layer was washed with water was dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by column chromatography

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

Procedure: 5-Fluoro-2-hydroxybenzoic acid (344 mg), 1-ethyl-3-(3-dimethylaminopropylcarbodiimide hydrochloride (420 mg), 1-hydroxybenzotriazole hydrate (337 mg), and ethanol (2 ml) were dissolved in N,N-dimethylformamide to prepare a solution which was then stirred at room temperature overnight. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by column chromatography using acetone-hexane to give ethyl 5-fluorosalicylate (191 mg, yield 28%). to prepare a solution which the mixture was extracted with ethyl acetate The ethyl acetate layer was then washed with water was dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by column chromatography