2-(chloromethyl)-1-benzofuran

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (+)-2-[2-(N,N-dimethylamino)ethyl]-6-hydroxytetralin (0.217 g) in DMF (5 ml) was added sodium hydride (60% in oil, 0.052 g) at room temperature. The reaction mixture was stirred at 50° C. for one hr and cooled to 0° C. A solution of 2-chloromethylbenzofuran (0.187 g) in THF (5 ml) was added to the solution. The reaction mixture was stirred at 0° C. for one hr, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried, and concentrated. The residue was purified by alumina column chromatography (eluent: ethyl acetate:hexane=1:4) and recrystallized from ethyl acetate-hexane to obtain the titled compound (17 mg). cooled to 0° C The reaction mixture was stirred at 0° C. for one hr extracted with ethyl acetate The organic layer was washed with water and saturated aqueous sodium chloride dried concentrated The residue was purified by alumina column chromatography (eluent: ethyl acetate:hexane=1:4) recrystallized from ethyl acetate-hexane

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

Procedure: 2-(Chloromethyl) benzofuran (2.77 g, 16.63 mmol) was dissolved in aqueous methylamine (40 mL, 40 wt % in H2O) at 10° C. under a nitrogen atmosphere. After 10 minutes, the reaction mixture was warmed to room temperature and stirring was continued for 72 hours. The mixture was diluted with water and extracted with dichloromethane. The organic phase was dried (MgSO4) and concentrated to afford crude product which was purified by flash column chromatography (10% methanol/dichloromethane) to afford 1.00 g (37%) of pure product as a pale yellow oil. was continued for 72 hours extracted with dichloromethane The organic phase was dried (MgSO4) concentrated to afford crude product which was purified by flash column chromatography (10% methanol/dichloromethane)

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

Procedure: 2-(Chloromethyl) benzofuran (2.77 g, 16.63 mmol) was dissolved in aqueous methylamine (40 mL, 40 wt % in H2O) at 10° C. under a nitrogen atmosphere. After 10 minutes, the reaction mixture was warmed to room temperature and stirring was continued for 72 hours. The mixture was diluted with water and extracted with dichloromethane. The organic phase was dried (MgSO4) and concentrated to afford crude product which was purified by flash column chromatography (10% methanol/dichloromethane) to afford 1.00 g (37%) of pure product as a pale yellow oil. was continued for 72 hours extracted with dichloromethane The organic phase was dried (MgSO4) concentrated to afford crude product which was purified by flash column chromatography (10% methanol/dichloromethane)

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

Procedure: Thionyl chloride (5.14 mL, 70.46 mmol) was added dropwise to a solution of benzofuran-2-methanol (3.58 g, 23.48 mmol) and pyridine (10 drops) in dichloromethane (60 mL). Stirring was continued at room temperature for 18 hours. The mixture was carefully diluted with water and extracted with methylene chloride. The organic extracts were washed with aqueous sodium bicarbonate, dried (MgSO4) and concentrated to afford crude product which was purified by flash column chromatography (10% ethyl acetate/hexanes) to afford 2.77 g (69%) of pure product as a yellow oil. extracted with methylene chloride The organic extracts were washed with aqueous sodium bicarbonate dried (MgSO4) concentrated to afford crude product which was purified by flash column chromatography (10% ethyl acetate/hexanes)

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

Procedure: 2-(Chloromethyl) benzofuran (2.77 g, 16.63 mmol) was dissolved in aqueous methylamine (40 mL, 40 wt % in H2O) at 10° C. under a nitrogen atmosphere. After 10 minutes, the reaction mixture was warmed to room temperature and stirring was continued for 72 hours. The mixture was diluted with water and extracted with methylene chloride. The organic phase was dried (MgSO4) and concentrated to afford crude product which was purified by flash column chromatography (10% MeOH/CH2Cl2) to afford 1.00 g (37%) of pure product as a pale yellow oil. was continued for 72 hours extracted with methylene chloride The organic phase was dried (MgSO4) concentrated to afford crude product which was purified by flash column chromatography (10% MeOH/CH2Cl2)

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

Procedure: Thionyl chloride (5.14 mL, 70.46 mmol) was added dropwise to a solution of benzofuran-2-methanol (3.58 g, 23.48 mmol) and pyridine (10 drops) in methylene chloride (60 mL). Stirring was continued at room temperature for 18 hours. The mixture was carefully diluted with water and extracted with methylene chloride. The organic extracts were washed with aqueous sodium bicarbonate, dried (MgSO4) and concentrated to afford crude product which was purified by flash column chromatography (10% EtOAc/hexanes) to afford 2.77 g (69%) of pure product as a yellow oil. extracted with methylene chloride The organic extracts were washed with aqueous sodium bicarbonate dried (MgSO4) concentrated to afford crude product which was purified by flash column chromatography (10% EtOAc/hexanes)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (+)-2-[2-(N,N-dimethylamino)ethyl]-6-hydroxytetralin (0.217 g) in DMF (5 ml) was added sodium hydride (60% in oil, 0.052 g) at room temperature. The reaction mixture was stirred at 50° C. for one hr and cooled to 0° C. A solution of 2-chloromethylbenzofuran (0.187 g) in THF (5 ml) was added to the solution. The reaction mixture was stirred at 0° C. for one hr, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried, and concentrated. The residue was purified by alumina column chromatography (eluent:ethyl acetate:hexane=1:4) and recrystallized from ethyl acetate-hexane to obtain the titled compound (17 mg). cooled to 0° C The reaction mixture was stirred at 0° C. for one hr extracted with ethyl acetate The organic layer was washed with water and saturated aqueous sodium chloride dried concentrated The residue was purified by alumina column chromatography (eluent:ethyl acetate:hexane=1:4) recrystallized from ethyl acetate-hexane

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

Procedure: A three-necked flask is charged with 33.2 g of 2-benzofuranylmethanol dissolved in 450 ml of anhydrous chloroform, 48.8 ml of thionyl chloride are then introduced dropwise and the temperature is raised gently to reflux and maintained for 3 hours 30 minutes. The reaction medium is then cooled and poured into 1 1 of water, and is thereafter diluted with 500 ml of dichloromethane. After settling has taken place, the organic phase is washed to neutrality and dried over anhydrous magnesium sulfate, the solvent is evaporated off and the residue is distilled under vacuum to obtain the expected compound. the temperature is raised gently to reflux maintained for 3 hours 30 minutes The reaction medium is then cooled the organic phase is washed to neutrality dried over anhydrous magnesium sulfate the solvent is evaporated off the residue is distilled under vacuum

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

Procedure: A three-necked flask is charged with 33.2 g of 2-benzofuranylmethanol dissolved in 450 ml of anhydrous chloroform, 48.8 ml of thionyl chloride are then introduced dropwise and the temperature is raised gently to reflux and maintained for 3 hours 30 minutes. The reaction medium is then cooled and poured into 1 1 of water, and is thereafter diluted with 500 ml of dichloromethane. After settling has taken place, the organic phase is washed to neutrality and dried over anhydrous magnesium sulfate, the solvent is evaporated off and the residue is distilled under vacuum to obtain the expected compound. the temperature is raised gently to reflux maintained for 3 hours 30 minutes The reaction medium is then cooled the organic phase is washed to neutrality dried over anhydrous magnesium sulfate the solvent is evaporated off the residue is distilled under vacuum

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (+)-2-[2-(N,N-dimethylamino)ethyl]-6-hydroxytetralin (0.217 g) in DMF (5 ml) was added sodium hydride (60% in oil, 0.052 g) at room temperature. The reaction mixture was stirred at 50° C. for one hr and cooled to 0° C. A solution of 2-chloromethylbenzofuran (0.187 g) in THF (5 ml) was added to the solution. The reaction mixture was stirred at 0° C. for one hr, diluted with water, and extracted with ethyl acetate. The organic layer was washed with water and saturated aqueous sodium chloride, dried, and concentrated. The residue was purified by alumina column chromatography (eluent: ethyl acetate:hexane=1:4) and recrystallized from ethyl acetate-hexane to obtain the titled compound (17 mg). cooled to 0° C The reaction mixture was stirred at 0° C. for one hr extracted with ethyl acetate The organic layer was washed with water and saturated aqueous sodium chloride dried concentrated The residue was purified by alumina column chromatography (eluent: ethyl acetate:hexane=1:4) recrystallized from ethyl acetate-hexane