5-bromo-7-methoxy-1H-indole-2,3-dione

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

Procedure: A stirred mixture of 5-bromo-7-methoxyindoline-2,3-dione (3.6 g, 14 mmol), p-TSA (1.14 g, 6 mmol) and toluene (100 mL) was refluxed using a Dean-Stark apparatus for 0.2 h. Ethylene glycol (9.3 g, 150 mmol, 10.7 eq.) was added and refluxed using a Dean-Stark apparatus for another 2 hours. The mixture was cooled and concentrated to 20 mL. EtOAc (100 mL) was added, washed with water (20 mL), brine (50 mL×2), dried over Na2SO4, filtered and concentrated under reduced pressure. Purified by column (CH2CL2/EtOAc=8:1) to give the desired product as a light brown solid (0.21 g, crude, 5%). 1H NMR (400 MHz, DMSO-d6): δH 10.66 (s, 1H), 7.48 (s, 1H), 7.26-7.27 (m, 1H), 7.13-7.14 (m, 1H), 4.25-4.31 (m, 4H), 3.86 (s, 3H). MS (ESI) m/e [M+1]+ 300/302. was refluxed for 0.2 h refluxed for another 2 hours The mixture was cooled concentrated to 20 mL EtOAc (100 mL) was added washed with water (20 mL), brine (50 mL×2) dried over Na2SO4 filtered concentrated under reduced pressure Purified by column (CH2CL2/EtOAc=8:1)

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

Procedure: A stirred mixture of 5-bromo-7-methoxyindoline-2,3-dione (3.6 g, 14 mmol), p-TSA (1.14 g, 6 mmol) and toluene (100 mL) was refluxed using a Dean-Stark apparatus for 0.2 h. Ethylene glycol (9.3 g, 150 mmol, 10.7 eq.) was added and refluxed using a Dean-Stark apparatus for another 2 hours. The mixture was cooled and concentrated to 20 mL. EtOAc (100 mL) was added, washed with water (20 mL), brine (50 mL×2), dried over Na2SO4, filtered and concentrated under reduced pressure. Purified by column (CH2CL2/EtOAc=8:1) to give the desired product as a light brown solid (0.21 g, crude, 5%). 1H NMR (400 MHz, DMSO-d6): δH 10.66 (s, 1H), 7.48 (s, 1H), 7.26-7.27 (m, 1H), 7.13-7.14 (m, 1H), 4.25-4.31 (m, 4H), 3.86 (s, 3H). MS (ESI) m/e [M+1]+ 300/302. was refluxed for 0.2 h refluxed for another 2 hours The mixture was cooled concentrated to 20 mL EtOAc (100 mL) was added washed with water (20 mL), brine (50 mL×2) dried over Na2SO4 filtered concentrated under reduced pressure Purified by column (CH2CL2/EtOAc=8:1)

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

Procedure: To concentrated H2SO4 (30 ml) at 65° C. was added N-(4-bromo-2-methoxyphenyl)-2-(hydroxyimino)acetamide (5.55 g, 20 mmol) portionwise. The mixture was heated at 90° C. for 1.5 h. The mixture was cooled to room temperature, poured onto ice, and stirred for 10 min. The solid was collected by filtration, washed with water, and air dried to afford 5-Bromo-7-methoxyindoline-2,3-dione (3.6 g, crude, 70% yield). This material was used without further purification. 1H NMR (400 MHz, DMSO-d6): δH 7.93 (s, 1H), 7.38 (s, 1H), 3.94 (s, 3H). MS (ESI) m/e [M+1]+ 256, 258. The mixture was cooled to room temperature poured onto ice The solid was collected by filtration washed with water, and air dried

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

Procedure: A stirred mixture of 5-bromo-7-methoxyindoline-2,3-dione (3.6 g, 14 mmol), p-TSA (1.14 g, 6 mmol) and toluene (100 mL) was refluxed using a Dean-Stark apparatus for 0.2 h. Ethylene glycol (9.3 g, 150 mmol, 10.7 eq.) was added and refluxed using a Dean-Stark apparatus for another 2 hours. The mixture was cooled and concentrated to 20 mL. EtOAc (100 mL) was added, washed with water (20 mL), brine (50 mL×2), dried over Na2SO4, filtered and concentrated under reduced pressure. Purified by column (CH2CL2/EtOAc=8:1) to give the desired product as a light brown solid (0.21 g, crude, 5%). 1H NMR (400 MHz, DMSO-d6): δH 10.66 (s, 1H), 7.48 (s, 1H), 7.26-7.27 (m, 1H), 7.13-7.14 (m, 1H), 4.25-4.31 (m, 4H), 3.86 (s, 3H). MS (ESI) m/e [M+1]+ 300/302. was refluxed for 0.2 h refluxed for another 2 hours The mixture was cooled concentrated to 20 mL EtOAc (100 mL) was added washed with water (20 mL), brine (50 mL×2) dried over Na2SO4 filtered concentrated under reduced pressure Purified by column (CH2CL2/EtOAc=8:1)

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

Procedure: To concentrated H2SO4 (30 ml) at 65° C. was added N-(4-bromo-2-methoxyphenyl)-2-(hydroxyimino)acetamide (5.55 g, 20 mmol) portionwise. The mixture was heated at 90° C. for 1.5 h. The mixture was cooled to room temperature, poured onto ice, and stirred for 10 min. The solid was collected by filtration, washed with water, and air dried to afford 5-Bromo-7-methoxyindoline-2,3-dione (3.6 g, crude, 70% yield). This material was used without further purification. 1H NMR (400 MHz, DMSO-d6): δH 7.93 (s, 1H), 7.38 (s, 1H), 3.94 (s, 3H). MS (ESI) m/e [M+1]+ 256, 258. The mixture was cooled to room temperature poured onto ice The solid was collected by filtration washed with water, and air dried