4-bromo-3,5-dimethoxybenzaldehyde

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:

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

Procedure: 4-bromo-3,5-dimethoxybenzaldehyde (3 g) was dissolved in toluene (50 mL) and ethylene glycol (6.8 mL) and a catalytic amount of p-TSA were added. The mixture was refluxed overnight using a Dean Stark apparatus and evaporated. The residue was purified by column chromatography (silica gel; eluent hexane/AcOEt 5:1 to 2:1) to give 4-bromo-3,5-dimethoxybenzaldehyde ethylene acetal (2.63 g). The mixture was refluxed overnight evaporated The residue was purified by column chromatography (silica gel; eluent hexane/AcOEt 5:1 to 2:1)

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

Procedure: 4-bromo-3,5-dimethoxybenzaldehyde (3 g) was dissolved in toluene (50 mL) and ethylene glycol (6.8 mL) and a catalytic amount of p-TSA were added. The mixture was refluxed overnight using a Dean Stark apparatus and evaporated. The residue was purified by column chromatography (silica gel; eluent hexane/AcOEt 5:1 to 2:1) to give 4-bromo-3,5-dimethoxybenzaldehyde ethylene acetal (2.63 g). The mixture was refluxed overnight evaporated The residue was purified by column chromatography (silica gel; eluent hexane/AcOEt 5:1 to 2:1)

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

Procedure: A solution of 4-bromo-3,5-dimethoxybenzaldehyde (5.04 g, 20.57 mmole) and toluenesulfonylmethyl isocyanide (4.22 g, 21.6 mmole) in MeOH (50 ml) was heated at reflux for 3 hrs. After evaporation to near dryness, H2O (50 ml) and EtOAc (200 ml) were added with stirring. The organic layer was separated and washed with brine (50 ml), dried over Na2SO4 and concentrated in vacuo. Et2O (50 ml) was added with swirling and the product was collected by filtration, washed with Et2O (2×25 ml) and dried giving 5-(4-bromo-3,5-dimethoxyphenyl)oxazole as a pale yellow solid (2.25 g, 39% yield). at reflux for 3 hrs After evaporation were added The organic layer was separated washed with brine (50 ml) dried over Na2SO4 concentrated in vacuo Et2O (50 ml) was added the product was collected by filtration washed with Et2O (2×25 ml) dried

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

Procedure: A solution of 4-bromo-3,5-dimethoxybenzaldehyde (5.04 g, 20.57 mmole) and toluenesulfonylmethyl isocyanide (4.22 g, 21.6 mmole) in MeOH (50 ml) was heated at reflux for 3 hrs. After evaporation to near dryness, H2O (50 ml) and EtOAc (200 ml) were added with stirring. The organic layer was separated and washed with brine (50 ml), dried over Na2SO4 and concentrated in vacuo. Et2O (50 ml) was added with swirling and the product was collected by filtration, washed with Et2O (2×25 ml) and dried giving 5-(4-bromo-3,5-dimethoxyphenyl)oxazole as a pale yellow solid (2.25 g, 39% yield). at reflux for 3 hrs After evaporation were added The organic layer was separated washed with brine (50 ml) dried over Na2SO4 concentrated in vacuo Et2O (50 ml) was added the product was collected by filtration washed with Et2O (2×25 ml) dried

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

Procedure: An oven-dried flask under argon was charged with 4-bromo-3,5-dimethoxybenzaldehyde (5.0 g, 20.4 mmol) and anhydrous THF (30 mL). The mixture was cooled over ice then a solution of ethyl magnesium bromide (3.0 M in diethyl ether, 8.2 mL, 24.5 mmol) was added dropwise from an addition funnel over a period of 45 min. After stirring for 20 min, the mixture was allowed to warm to room temperature and stirred for 19 hrs. After quenching with a solution of aqueous NH4Cl, it was diluted with H2O and EtOAc then cooled over an ice bath. After the mixture was cooled, the layers were separated. The organics were washed with H2O and brine then dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in CH2Cl2 and concentrated in vacuo again to give 1-(4-bromo-3,5-dimethoxyphenyl)propan-1-ol as a clear oil (5.43 g, 97% yield). The product was used without further purification. The mixture was cooled over ice stirred for 19 hrs After quenching with a solution of aqueous NH4Cl, it was diluted with H2O and EtOAc then cooled over an ice bath After the mixture was cooled the layers were separated The organics were washed with H2O and brine then dried over Na2SO4 concentrated in vacuo The residue was dissolved in CH2Cl2 concentrated in vacuo again

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

Procedure: To an oven-dried flask under argon was added 4-bromo-3,5-dimethoxybenzaldehyde (1.0 g, 4.08 mmol), absolute EtOH (34 mL), p-toluenesulfonylmethyl isocyanide (0.78 g, 4.0 mmol) and KCN (0.035 g, 0.54 mmol). The mixture was stirred for 19 hours at room temperature then concentrated in vacuo to give 5-(4-bromo-3,5-dimethoxyphenyl)-4-tosyl-4,5-dihydrooxazole which was used in the next synthetic step without purification. then concentrated in vacuo

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

Procedure: To an oven-dried flask under argon was added 4-bromo-3,5-dimethoxybenzaldehyde (1.0 g, 4.08 mmol), absolute EtOH (34 mL), p-toluenesulfonylmethyl isocyanide (0.78 g, 4.0 mmol) and KCN (0.035 g, 0.54 mmol). The mixture was stirred for 19 hours at room temperature then concentrated in vacuo to give 5-(4-bromo-3,5-dimethoxyphenyl)-4-tosyl-4,5-dihydrooxazole which was used in the next synthetic step without purification. then concentrated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An oven-dried flask under argon was charged with 4-bromo-3,5-dimethoxybenzaldehyde (10.08 g, 41.1 mmol) and anhydrous THF (70 mL). The mixture was cooled over a −78° C. bath then a solution of MeMgBr (3.0 M in diethyl ether, 17.8 mL, 53.4 mmol) was added dropwise from an addition funnel over a period of 45 min. After stirring for 20 min, the mixture was allowed to warm to room temperature and stirred for 19 hours. After quenching with a solution of aqueous NH4Cl, it was diluted with H2O and EtOAc then cooled over an ice bath. After the mixture was cooled, the layers were separated. The organics were washed with H2O and brine then dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in dichloromethane and concentrated in vacuo again to give 1-(4-bromo-3,5-dimethoxyphenyl)ethanol as a white solid (10.8 g, quantitiative yield). The product was used without further purification. to warm to room temperature stirred for 19 hours After quenching with a solution of aqueous NH4Cl, it was diluted with H2O and EtOAc then cooled over an ice bath After the mixture was cooled the layers were separated The organics were washed with H2O and brine then dried over Na2SO4 concentrated in vacuo The residue was dissolved in dichloromethane concentrated in vacuo again to give