1-chloro-2-phenoxybenzene

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

Procedure: In a stream of nitrogen gas, 2-chlorodiphenyl ether (10.23 g, 0.05 mol) in dry THF (20 ml) was dropwise added to a mixture of magnesium (1.34 g, 0.055 mol) and ethyl bromide (0.19 ml) in dry THF (15 ml) under reflux over 30 minutes. After further reflux for 6 hours, the reaction mixture was diluted with dry THF (15 ml) and cooled below 20° C. This mixture was dropwise added to oxalyl chloride (7.62 g, 0.06 mol) in dry THF (100 ml) at -10° to 0° C. over 15 minutes, followed by stirring at -10° to 0° C., and methylamine gas was introduced into the mixture, followed by stirring at room temperature for 15 minutes. After completion of the reaction, 1N HCl (100 ml) was added to the reaction mixture which was then extracted with toluene (300 ml). The extract was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to give N-methyl-2-(2-phenoxyphenyl)-2-oxoacetamide (8.07 g) as colorless crystals. The mother liquor was purified by silica gel chromatography (ethyl acetate/hexane) to give the objective compound (1.42 g). The total yield was 9.49 g (74%). under reflux over 30 minutes After further reflux for 6 hours cooled below 20° C by stirring at room temperature for 15 minutes was added to the reaction mixture which was then extracted with toluene (300 ml) The extract was washed with water and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate/hexane

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

Procedure: In a stream of nitrogen gas, 2-chlorodiphenyl ether (10.23 g, 0.05 mol) in dry THF (20 ml) was dropwise added to a mixture of magnesium (1.34 g, 0.055 mol) and ethyl bromide (0.19 ml) in dry THF (15 ml) under reflux over 30 minutes. After further reflux for 6 hours, the reaction mixture was diluted with dry THF (15 ml) and cooled below 20° C. This mixture was dropwise added to oxalyl chloride (7.62 g, 0.06 mol) in dry THF (100 ml) at -10° to 0° C. over 15 minutes, followed by stirring at -10° to 0° C., and methylamine gas was introduced into the mixture, followed by stirring at room temperature for 15 minutes. After completion of the reaction, 1N HCl (100 ml) was added to the reaction mixture which was then extracted with toluene (300 ml). The extract was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to give N-methyl-2-(2-phenoxyphenyl)-2-oxoacetamide (8.07 g) as colorless crystals. The mother liquor was purified by silica gel chromatography (ethyl acetate/hexane) to give the objective compound (1.42 g). The total yield was 9.49 g (74%). under reflux over 30 minutes After further reflux for 6 hours cooled below 20° C by stirring at room temperature for 15 minutes was added to the reaction mixture which was then extracted with toluene (300 ml) The extract was washed with water and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate/hexane

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

Procedure: In a stream of nitrogen gas, 2-chlorodiphenyl ether (10.23 g, 0.05 mol) in dry THF (20 ml) was dropwise added to a mixture of magnesium (1.34 g, 0.055 mol) and ethyl bromide (0.19 ml) in dry THF (15 ml) under reflux over 30 minutes. After further reflux for 6 hours, the reaction mixture was diluted with dry THF (15 ml) and cooled below 20° C. This mixture was dropwise added to oxalyl chloride (7.62 g, 0.06 mol) in dry THF (100 ml) at -10° to 0° C. over 15 minutes, followed by stirring at -10° to 0° C., and methylamine gas was introduced into the mixture, followed by stirring at room temperature for 15 minutes. After completion of the reaction, 1N HCl (100 ml) was added to the reaction mixture which was then extracted with toluene (300 ml). The extract was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to give N-methyl-2-(2-phenoxyphenyl)-2-oxoacetamide (8.07 g) as colorless crystals. The mother liquor was purified by silica gel chromatography (ethyl acetate/hexane) to give the objective compound (1.42 g). The total yield was 9.49 g (74%). under reflux over 30 minutes After further reflux for 6 hours cooled below 20° C by stirring at room temperature for 15 minutes was added to the reaction mixture which was then extracted with toluene (300 ml) The extract was washed with water and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate/hexane

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

Procedure: In a stream of nitrogen gas, 2-chlorodiphenyl ether (10.23 g, 0.05 mol) in dry THF (20 ml) was dropwise added to a mixture of magnesium (1.34 g, 0.055 mol) and ethyl bromide (0.19 ml) in dry THF (15 ml) under reflux over 30 minutes. After further reflux for 6 hours, the reaction mixture was diluted with dry THF (15 ml) and cooled below 20° C. This mixture was dropwise added to oxalyl chloride (7.62 g, 0.06 mol) in dry THF (100 ml) at -10° to 0° C. over 15 minutes, followed by stirring at -10° to 0° C., and methylamine gas was introduced into the mixture, followed by stirring at room temperature for 15 minutes. After completion of the reaction, 1N HCl (100 ml) was added to the reaction mixture which was then extracted with toluene (300 ml). The extract was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to give N-methyl-2-(2-phenoxyphenyl)-2-oxoacetamide (8.07 g) as colorless crystals. The mother liquor was purified by silica gel chromatography (ethyl acetate/hexane) to give the objective compound (1.42 g). The total yield was 9.49 g (74%). under reflux over 30 minutes After further reflux for 6 hours cooled below 20° C by stirring at room temperature for 15 minutes was added to the reaction mixture which was then extracted with toluene (300 ml) The extract was washed with water and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate/hexane

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 85% Potassium hydroxide powders (2.18 g; 0.033 mol, 1.1 equimolar amount) were added to phenol (4.23 g; 0.045 mol, 1.5 eq.) under heating, and 1,2-dichlorobenzene (4.41 g; 0.03 mol) and copper(I) iodide (0.29 g; 0.0015 mol) were added thereto, followed by stirring at 160° C. for 24 hours. The reaction mixture was diluted with water and extracted with ether. The extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with a mixture of benzene and n-hexane to give 3.48 g (yield, 56.7%) of 2-chlorodiphenyl ether as colorless crystals. m.p., 33° to 41° C. under heating extracted with ether The extract was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography with a mixture of benzene and n-hexane

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

Procedure: In a stream of nitrogen gas, 2-chlorodiphenyl ether (10.23 g, 0.05 mol) in dry THF (20 ml) was dropwise added to a mixture of magnesium (1.34 g, 0.055 mol) and ethyl bromide (0.19 ml) in dry THF (15 ml) under reflux over 30 minutes. After further reflux for 6 hours, the reaction mixture was diluted with dry THF (15 ml) and cooled below 20° C. This mixture was dropwise added to oxalyl chloride (7.62 g, 0.06 mol) in dry THF (100 ml) at -10° to 0° C. over 15 minutes, followed by stirring at -10° to 0° C., and methylamine gas was introduced into the mixture, followed by stirring at room temperature for 15 minutes. After completion of the reaction, in 1N HCl (100 ml) was added to the reaction mixture which was then extracted with toluene (300 ml). The extract was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to give N-methyl-2-(2-phenoxyphenyl)-2-oxoacetamide (8.07 g) as colorless crystals. The mother liquor was purified by silica gel chromatography (ethyl acetate/hexane) to give the objective compound (1.42 g). The total yield was 9.49 g (74%). under reflux over 30 minutes After further reflux for 6 hours cooled below 20° C by stirring at room temperature for 15 minutes After completion of the reaction was then extracted with toluene (300 ml) The extract was washed with water and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate/hexane

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

Procedure: In a stream of nitrogen gas, 2-chlorodiphenyl ether (10.23 g, 0.05 mol) in dry THF (20 ml) was dropwise added to a mixture of magnesium (1.34 g, 0.055 mol) and ethyl bromide (0.19 ml) in dry THF (15 ml) under reflux over 30 minutes. After further reflux for 6 hours, the reaction mixture was diluted with dry THF (15 ml) and cooled below 20° C. This mixture was dropwise added to oxalyl chloride (7.62 g, 0.06 mol) in dry THF (100 ml) at -10° to 0° C. over 15 minutes, followed by stirring at -10° to 0° C., and methylamine gas was introduced into the mixture, followed by stirring at room temperature for 15 minutes. After completion of the reaction, 1N HCl (100 ml) was added to the reaction mixture which was then extracted with toluene (300 ml). The extract was washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate/hexane to give N-methyl-2-(2-phenoxyphenyl)-2-oxoacetamide (8.07 g) as colorless crystals. The mother liquor was purified by silica gel chromatography (ethyl acetate/hexane) to give the objective compound (1.42 g). The total yield was 9.49 g (74%). under reflux over 30 minutes After further reflux for 6 hours cooled below 20° C by stirring at room temperature for 15 minutes was added to the reaction mixture which was then extracted with toluene (300 ml) The extract was washed with water and brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was recrystallized from ethyl acetate/hexane