(4-bromo-2-methylphenyl)hydrazine

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: 200 mg of 1-(4-bromo-2-methylphenyl)hydrazine was suspended in 10.0 mL EtOH propionaldehyde (678 μL) was added. The reaction became clear after the addition of propionaldehyde. The resulting solution was then stirred at room temperature for 45 minutes. The reaction was concentrated and zinc(II)chloride (1070.0 mg) was added and the mixture was heated at 170° C. for 30 minutes. The melting mixture was then cooled to room temperature, and diluted with 10% HCl solution. The solution was then extracted with dichloromethane, dried over magnesium sulfate, filtered and concentrated. The residue was flash chromatographed (0-10% EtOAc/Haptanes gradient) to obtain 317.0 mg of 5-bromo-3,7-dimethyl-1H-indole. LC-MS @ 222.1 (M−1) was added The reaction was concentrated zinc(II)chloride (1070.0 mg) was added the mixture was heated at 170° C. for 30 minutes The melting mixture was then cooled to room temperature diluted with 10% HCl solution The solution was then extracted with dichloromethane dried over magnesium sulfate filtered concentrated chromatographed (0-10% EtOAc/Haptanes gradient)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-bromo-2-methylaniline (2.0 g) was dissolved in conc. HCl (10 mL) and heated to 80° C. for 30 minutes. The reaction was cooled to 5° C. and a solution of sodium nitrite (781.0 mg in 4.0 mL of water) was added over 10 minutes. The resulting mixture was then stirred at 5° C. for 30 minutes. A solution of tin(II)chloride (15.3 g in 8 mL of concentrated HCl) was added over 10 minutes, and the resulting solution was stirred at room temperature for 45 minutes. The reaction was made basic with 50% NaOH solution and a white precipitate formed. The solid was filtered and the filtrate extracted with dichloromethane. The organic extract was dried over magnesium sulfate, filtered and concentrated to yield 1.08 g (50%) of 1-(4-bromo-2-methylphenyl)hydrazine as a white solid. LC-MS @ 201.1 (M+1) The reaction was cooled to 5° C. the resulting solution was stirred at room temperature for 45 minutes a white precipitate formed The solid was filtered the filtrate extracted with dichloromethane The organic extract was dried over magnesium sulfate filtered concentrated

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

Procedure: To a suspenstion of (4-bromo-2-methylphenyl)hydrazine (1.44 g, 7.16 mmol) in ethanol (10 mL) was added propionaldehyde (0.68 mL, 9.3 mmol). The solution became clear and the mixture was stirred at room temperature for 45 minutes. The solvents were removed and anhydrous ZnCl2 (1.07 g, 7.88 mmol) was added and the mixture was heated at 170° C. for 30 minutes. The mixture was cooled to room temperature, diluted with 10% HCl, extracted with CH2Cl2 and the organic extract was dried over MgSO4. After filtration and concentration, the residue was purified by CombiFlash (0-10% EtOAc/heptane) to provide 5-bromo-3,7-dimethyl-1H-indole (317 mg, 20%). The solvents were removed the mixture was heated at 170° C. for 30 minutes The mixture was cooled to room temperature extracted with CH2Cl2 the organic extract was dried over MgSO4 After filtration and concentration the residue was purified by CombiFlash (0-10% EtOAc/heptane)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-2-methylaniline (2.00 g, 10.8 mmol) was dissolved in conc. HCl (10 mL) and heated to 80° C. for 30 minutes. The reaction was then cooled to 5° C. and a solution of NaNO2 (781 mg, 10.8 mmol) in water (4 mL) was added over 10 minutes. The resulting mixture was stirred at 5° C. for 30 minutes before addition of SnCl2 (15.3 g, 80.6 mmol) in conc. HCl (8 mL) over 10 minutes. The mixture was stirred at room temperature for 45 minutes before addition of 50% aqueous NaOH. The resulting precipitate was isolated by filtration and the filtrate was extracted with CH2Cl2. The combined organic phases were dried over MgSO4, filtered and concentrated to provide (4-bromo-2-methylphenyl)hydrazine (1.08 g, 50%). The reaction was then cooled to 5° C. The resulting precipitate was isolated by filtration the filtrate was extracted with CH2Cl2 The combined organic phases were dried over MgSO4 filtered concentrated

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

Procedure: Potassium tert-butoxide (20 ml, 1M in tert-butanol, 20.0 mmol) was added to 1-(4-bromo-2-methylphenyl)hydrazine (J. Chem. Soc. 109; 1916; 582)(2.01 g, 10.0 mmol) to give a dark brown suspension. Ethyl propiolate (1.02 ml, 10 mmol) was then added dropwise over 10 minutes, with cooling, and once addition was complete, the reaction was heated under reflux for 4 hours. The reaction was diluted with water (200 ml) and this mixture washed with dichloromethane (2×50 ml). The aqueous phase was acidified using hydrochloric acid (2N), extracted with dichloromethane (5×100 ml), these combined organic extracts dried (MgSO4), filtered and evaporated in vacuo. The crude product was purified by column chromatography on silica gel using dichloromethane:methanol (98:2) as eluant, and triturated with ether/di-isopropyl ether to give the title compound (615 mg, 24%) as a solid. to give a dark brown suspension with cooling once addition the reaction was heated under reflux for 4 hours this mixture washed with dichloromethane (2×50 ml) extracted with dichloromethane (5×100 ml) these combined organic extracts dried (MgSO4) filtered evaporated in vacuo The crude product was purified by column chromatography on silica gel triturated with ether/di-isopropyl ether