7-chloro-5-fluoro-1H-indole-2,3-dione

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:; See reaction.notes.procedure_details.

Procedure: A solution of 7-chloro-5-fluoro-1H-indole-2,3-dione (270 mg) in 1 M sodium hydroxide solution (5 mL) was treated with 30% hydrogen peroxide (5 mL) via dropwise addition. After one hour of stirring, the reaction was acidified with HCl to pH 1, and extracted three times with ethyl acetate. The combined organic layers were dried with sodium sulfate, and concentrated in vacuo to provide 200 mg of 2-amino-3-chloro-5-fluoro-benzoic acid. extracted three times with ethyl acetate The combined organic layers were dried with sodium sulfate concentrated in vacuo

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

Procedure: A solution of 7-chloro-5-fluoro-1H-indole-2,3-dione (270 mg) in 1 M sodium hydroxide solution (5 mL) was treated with 30% hydrogen peroxide (5 mL) via dropwise addition. After one hour of stirring, the reaction was acidified with HCl to pH 1, and extracted three times with ethyl acetate. The combined organic layers were dried with sodium sulfate, and concentrated in vacuo to provide 200 mg of 2-amino-3-chloro-5-fluoro-benzoic acid. extracted three times with ethyl acetate The combined organic layers were dried with sodium sulfate concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of lithium aluminium hydride (0.57 g, 15 mmol) in THF (20 mL) at 0° C. under Ar was added portionwise 7-chloro-5-fluoroindole-2,3-dione. The mixture was heated under reflux for 4 h, cooled to 0° C. and water (0.5 mL) was added. The mixture was stirred for 5 min then treated with aqueous sodium hydroxide solution (2 N, 0.5 mL) followed by water (0.5 mL) and filtered through a pad of celite®. The filter-cake was washed with tetrahydrofuran and the filtrate was concentrated in vacuo and purified by column chromatography [SiO2; heptane-ethyl acetate (3:1)] to give the product (0.31 g, 37% yield) as a blue-oil: IR νmax (film)/cm−1 3459, 1575, 1485, 1341, 1120 and 722; NMR δH (400 MHz, CDCl3) 6.55 (1H, t, J 2.5 Hz) 7.01 (1H, dd, J 9,2 Hz) 7.21 (1H, m) 7.29 (1H, t, J 2.5 Hz) 8.33 (1H, brs). The mixture was heated under reflux for 4 h filtered through a pad of celite® The filter-cake was washed with tetrahydrofuran the filtrate was concentrated in vacuo purified by column chromatography [SiO2; heptane-ethyl acetate (3:1)]

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

Procedure: N-(2-Chloro-4-fluorophenyl)-2-(hydroxyimino)-acetamide (5.4 g, 24.9 mmol) was added portionwise to conc. sulfuric acid (70 mL) at 70° C. The mixture was stirred for 1 h, poured onto ice-water (200 mL) and filtered. The filter-cake was dried in vacuo to give crude 7-chloro-5-fluoroindole-2,3-dione which was used immediately without further purification. poured onto ice-water (200 mL) filtered The filter-cake was dried in vacuo

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

Procedure: A solution of 7-chloro-5-fluoro-1H-indole-2,3-dione (270 mg) in 1 M sodium hydroxide solution (5 mL) was treated with 30% hydrogen peroxide (5 mL) via dropwise addition. After one hour of stirring, the reaction was acidified with HCl to pH 1, and extracted three times with ethyl acetate. The combined organic layers were dried with sodium sulfate, and concentrated in vacuo to provide 200 mg of 2-amino-3-chloro-5-fluoro-benzoic acid. extracted three times with ethyl acetate The combined organic layers were dried with sodium sulfate concentrated in vacuo

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

Procedure: A solution of 7-chloro-5-fluoro-1H-indole-2,3-dione (270 mg) in 1 M sodium hydroxide solution (5 mL) was treated with 30% hydrogen peroxide (5 mL) via dropwise addition. After one hour of stirring, the reaction was acidified with HCl to pH 1, and extracted three times with ethyl acetate. The combined organic layers were dried with sodium sulfate, and concentrated in vacuo to provide 200 mg of 2-amino-3-chloro-5-fluoro-benzoic acid. extracted three times with ethyl acetate The combined organic layers were dried with sodium sulfate concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of lithium aluminium hydride (0.57 g, 15 mmol) in THF (20 mL) at 0° C. under Ar was added portionwise 7-chloro-5-fluoroindole-2,3-dione. The mixture was heated under reflux for 4 h, cooled to 0° C. and water (0.5 mL) was added. The mixture was stirred for 5 min then treated with aqueous sodium hydroxide solution (2 N, 0.5 mL) followed by water (0.5 mL) and filtered through a pad of celite®. The filter-cake was washed with tetrahydrofuran and the filtrate was concentrated in vacuo and purified by column chromatography [SiO2; heptane-ethyl acetate (3:1)] to give the product (0.31 g, 37% yield) as a blue-oil: IR νmax (film)/cm−1 3459, 1575, 1485, 1341, 1120 and 722; NMR δH (400 MHz, CDCl3) 6.55 (1H, t, J 2.5 Hz) 7.01 (1H, dd, J 9,2 Hz) 7.21 (1H, m) 7.29 (1H, t, J 2.5 Hz) 8.33 (1H, brs). The mixture was heated under reflux for 4 h filtered through a pad of celite® The filter-cake was washed with tetrahydrofuran the filtrate was concentrated in vacuo purified by column chromatography [SiO2; heptane-ethyl acetate (3:1)]

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

Procedure: N-(2-Chloro-4-fluorophenyl)-2-(hydroxyimino)-acetamide (5.4 g, 24.9 mmol) was added portionwise to conc. sulfuric acid (70 mL) at 70° C. The mixture was stirred for 1 h, poured onto ice-water (200 mL) and filtered. The filter-cake was dried in vacuo to give crude 7-chloro-5-fluoroindole-2,3-dione which was used immediately without further purification. poured onto ice-water (200 mL) filtered The filter-cake was dried in vacuo