6-bromo-3-methyl-1,3-dihydroindol-2-one

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

Procedure: Sodium hydride (3.9 g) was suspended in dimethyl sulfoxide (24 mL), and diethyl methyl malonate (16 mL) was added at 0° C., and then the reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was heated to 100° C., and a solution of 2,5-dibromonitrobenzene (15.3 g) in dimethyl sulfoxide (17 mL) was added at 100° C., and then the reaction mixture was stirred at 100° C. for 5 hours. The reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethanol (75 mL), and tin (11.5 g) was added at room temperature. Concentrated hydrochloric acid (45 mL) was added at 0° C., and then the reaction mixture was heated at reflux for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (4.9 g) as a brown solid. The reaction mixture was heated to 100° C. the reaction mixture was stirred at 100° C. for 5 hours The reaction mixture was quenched with water extracted with ethyl acetate The obtained organic layer was washed with brine dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure The residue was dissolved in ethanol (75 mL) tin (11.5 g) was added at room temperature Concentrated hydrochloric acid (45 mL) was added at 0° C. the reaction mixture was heated at reflux for 2 hours After cooling to room temperature the reaction mixture was quenched with water extracted with ethyl acetate The obtained organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and brine dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography

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

Procedure: Sodium hydride (3.9 g) was suspended in dimethyl sulfoxide (24 mL), and diethyl methyl malonate (16 mL) was added at 0° C., and then the reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was heated to 100° C., and a solution of 2,5-dibromonitrobenzene (15.3 g) in dimethyl sulfoxide (17 mL) was added at 100° C., and then the reaction mixture was stirred at 100° C. for 5 hours. The reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethanol (75 mL), and tin (11.5 g) was added at room temperature. Concentrated hydrochloric acid (45 mL) was added at 0° C., and then the reaction mixture was heated at reflux for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (4.9 g) as a brown solid. The reaction mixture was heated to 100° C. the reaction mixture was stirred at 100° C. for 5 hours The reaction mixture was quenched with water extracted with ethyl acetate The obtained organic layer was washed with brine dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure The residue was dissolved in ethanol (75 mL) tin (11.5 g) was added at room temperature Concentrated hydrochloric acid (45 mL) was added at 0° C. the reaction mixture was heated at reflux for 2 hours After cooling to room temperature the reaction mixture was quenched with water extracted with ethyl acetate The obtained organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and brine dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography

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

Procedure: To 6-bromo-3-methyl-1,3-dihydro-2H-indol-2-one (11.2 g) were added acetic anhydride (12 ml) and xylene (120 ml), and the mixture was refluxed for 5 hours. After the reaction was complete, water was added to the reaction solution, and the mixture was extracted with ethyl acetate solution. This ethyl acetate solution was washed successively with water, a saturated aqueous sodium hydrogen carbonate solution and an aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1) to give the title compound (9.5 g) as a red solid. the mixture was refluxed for 5 hours the mixture was extracted with ethyl acetate solution This ethyl acetate solution was washed successively with water a saturated aqueous sodium hydrogen carbonate solution and an aqueous sodium chloride solution, dried over magnesium sulfate filtered concentrated The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1)

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

Procedure: To 2,6-dibromo-3-methyl-1H-indole (15.7 g) were added 3N aqueous sulfuric acid solution (100 ml) and dioxane (100 ml), and the mixture was refluxed for 5 hours. After the reaction was complete, water was added to the reaction solution, and the mixture was extracted with ethyl acetate solution. This ethyl acetate solution was washed with water and an aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1) to give the title compound (11.2 g) as a brown crystal. the mixture was refluxed for 5 hours the mixture was extracted with ethyl acetate solution This ethyl acetate solution was washed with water an aqueous sodium chloride solution, dried over magnesium sulfate filtered concentrated The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=4/1)

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

Procedure: Sodium hydride (3.9 g) was suspended in dimethyl sulfoxide (24 mL), and diethyl methyl malonate (16 mL) was added at 0° C., and then the reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was heated to 100° C., and a solution of 2,5-dibromonitrobenzene (15.3 g) in dimethyl sulfoxide (17 mL) was added at 100° C., and then the reaction mixture was stirred at 100° C. for 5 hours. The reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethanol (75 mL), and tin (11.5 g) was added at room temperature. Concentrated hydrochloric acid (45 mL) was added at 0° C., and then the reaction mixture was heated at reflux for 2 hours. After cooling to room temperature, the reaction mixture was quenched with water, and extracted with ethyl acetate. The obtained organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the titled compound (4.9 g) as a brown solid. The reaction mixture was heated to 100° C. the reaction mixture was stirred at 100° C. for 5 hours The reaction mixture was quenched with water extracted with ethyl acetate The obtained organic layer was washed with brine dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure The residue was dissolved in ethanol (75 mL) tin (11.5 g) was added at room temperature Concentrated hydrochloric acid (45 mL) was added at 0° C. the reaction mixture was heated at reflux for 2 hours After cooling to room temperature the reaction mixture was quenched with water extracted with ethyl acetate The obtained organic layer was washed with a saturated aqueous solution of sodium hydrogen carbonate and brine dried over anhydrous sodium sulfate filtered the filtrate was concentrated under reduced pressure The obtained residue was purified by silica gel column chromatography