4-bromo-3-methylbenzaldehyde

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

Procedure: 2.1 g (6.45 mmol, 1.5 eq) of methyl triphenylphosphoranylideneacetate are added to a solution of 900 mg of 4-bromo-3-methylbenzaldehyde in 5 ml of toluene. The reaction mixture is heated at 90° C. for 1 hour. The solvent is evaporated off and the residual oil is chromatographed on silica gel (8/2 heptane/ethyl acetate). 610 mg of methyl (E)-3-(4-bromo-3-methylphenyl)acrylate are obtained in oil form. Yield=55% over steps a, b and c. The solvent is evaporated off the residual oil is chromatographed on silica gel (8/2 heptane/ethyl acetate)

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

Procedure: 2.1 g (6.45 mmol, 1.5 eq) of methyl triphenylphosphoranylideneacetate are added to a solution of 900 mg of 4-bromo-3-methylbenzaldehyde in 5 ml of toluene. The reaction mixture is heated at 90° C. for 1 hour. The solvent is evaporated off and the residual oil is chromatographed on silica gel (8/2 heptane/ethyl acetate). 610 mg of methyl (E)-3-(4-bromo-3-methylphenyl)acrylate are obtained in oil form. Yield=55% over steps a, b and c. The solvent is evaporated off the residual oil is chromatographed on silica gel (8/2 heptane/ethyl acetate)

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

Procedure: 3.7 g (43 mmol, 10 eq) of manganese dioxide are added to a solution of 900 mg (4.3 mmol, 1 eq) of (4-bromo-3-methylphenyl)methanol in 8 mL of dichloromethane. The reaction mixture is stirred for 12 hours at room temperature. The solid is filtered off and the solvent is evaporated off. 900 mg of 4-bromo-3-methylbenzaldehyde are obtained in oil form and used in the following reaction without further purification. The solid is filtered off the solvent is evaporated off

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

Procedure: 3.7 g (43 mmol, 10 eq) of manganese dioxide are added to a solution of 900 mg (4.3 mmol, 1 eq) of (4-bromo-3-methylphenyl)methanol in 8 mL of dichloromethane. The reaction mixture is stirred for 12 hours at room temperature. The solid is filtered off and the solvent is evaporated off. 900 mg of 4-bromo-3-methylbenzaldehyde are obtained in oil form and used in the following reaction without further purification. The solid is filtered off the solvent is evaporated off

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

Procedure: To a solution of dimethyl sulfoxide (21.2 mL, 0.298 mol) in DCM (150 mL) was added oxalyl chloride (5.0 mL, 0.060 mol) at −78° C. under an atmosphere of nitrogen. The resulting mixture was stirred for 20 min. A solution of (4-bromo-3-methylphenyl)methanol (6.0 g, 0.030 mol) in methylene chloride (50 mL) was cannulated into the reaction flask. After stirring for 1.0 h, triethylamine (21 mL, 0.15 mol) was added. The reaction mixture was stirred at −78° C. for 1 h, warmed to room temperature for 1 h. The reaction was quenched with 1 N HCl solution, the aqueous phase was separated and extracted with methylene chloride once. The combined organic solutions were washed with brine, dried over sodium sulfate, filtered, concentrated in vacuo. The crude residue was purified by flash column chromatography to yield the desired product (5.7 g, 96%). 1H NMR (400 MHz, CDCl3): δ 9.96 (s, 1H), 7.73 (m, 1H), 7.71 (s, 1H), 7.55 (m, 1H), 2.49 (s, 3H). After stirring for 1.0 h The reaction mixture was stirred at −78° C. for 1 h The reaction was quenched with 1 N HCl solution the aqueous phase was separated extracted with methylene chloride once The combined organic solutions were washed with brine dried over sodium sulfate filtered concentrated in vacuo The crude residue was purified by flash column chromatography

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

Procedure: To a solution of dimethyl sulfoxide (21.2 mL, 0.298 mol) in DCM (150 mL) was added oxalyl chloride (5.0 mL, 0.060 mol) at −78° C. under an atmosphere of nitrogen. The resulting mixture was stirred for 20 min. A solution of (4-bromo-3-methylphenyl)methanol (6.0 g, 0.030 mol) in methylene chloride (50 mL) was cannulated into the reaction flask. After stirring for 1.0 h, triethylamine (21 mL, 0.15 mol) was added. The reaction mixture was stirred at −78° C. for 1 h, warmed to room temperature for 1 h. The reaction was quenched with 1 N HCl solution, the aqueous phase was separated and extracted with methylene chloride once. The combined organic solutions were washed with brine, dried over sodium sulfate, filtered, concentrated in vacuo. The crude residue was purified by flash column chromatography to yield the desired product (5.7 g, 96%). 1H NMR (400 MHz, CDCl3): δ 9.96 (s, 1H), 7.73 (m, 1H), 7.71 (s, 1H), 7.55 (m, 1H), 2.49 (s, 3H). After stirring for 1.0 h The reaction mixture was stirred at −78° C. for 1 h The reaction was quenched with 1 N HCl solution the aqueous phase was separated extracted with methylene chloride once The combined organic solutions were washed with brine dried over sodium sulfate filtered concentrated in vacuo The crude residue was purified by flash column chromatography

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

Procedure: To a mixture of 4-bromo-3-methyl-benzaldehyde (372 mg, 1.87 mmol) and hydroxylamine hydrochloride (306.5 mg, 4.41 mmol) in ethanol (5 mL) at rt was added Et3N (0.15 mL). The reaction mixture was heated under reflux for 2 h, cooled to rt and concentrated under reduced pressure. The residue was dissolved in EA (10 mL), washed with water, dried over MgSO4, filtered and concentrated under reduced pressure to give 4-bromo-3-methylbenzaldehyde oxime (384 mg; yield 96%) as a white solid. The reaction mixture was heated under reflux for 2 h concentrated under reduced pressure The residue was dissolved in EA (10 mL) washed with water dried over MgSO4 filtered concentrated under reduced pressure

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

Procedure: To a mixture of 4-bromo-3-methyl-benzaldehyde (372 mg, 1.87 mmol) and hydroxylamine hydrochloride (306.5 mg, 4.41 mmol) in ethanol (5 mL) at rt was added Et3N (0.15 mL). The reaction mixture was heated under reflux for 2 h, cooled to rt and concentrated under reduced pressure. The residue was dissolved in EA (10 mL), washed with water, dried over MgSO4, filtered and concentrated under reduced pressure to give 4-bromo-3-methylbenzaldehyde oxime (384 mg; yield 96%) as a white solid. The reaction mixture was heated under reflux for 2 h concentrated under reduced pressure The residue was dissolved in EA (10 mL) washed with water dried over MgSO4 filtered concentrated under reduced pressure

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

Procedure: To a solution of (4-bromo-3-methylphenyl)methanol (420 mg, 2.09 mmol) in DCM (6 mL) at rt was added MnO2 (1.82 g, 20.9 mmol). The reaction mixture was stirred for 12 h, filtered and concentrated under reduced pressure to give 4-bromo-3-methyl-benzaldehyde (372 mg; yield 89%) as an oil. filtered concentrated under reduced pressure