2-ethoxy-1,4-difluorobenzene

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

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

Procedure: Oxalyl chloride (1.89 mL, 0.0220 mol) and N,N-dimethylformamide (0.03 mL) were added to 5-bromo-2-chlorobenzoic acid (5.0 g, 0.0212 mol) in chloroform (10 mL) and stirred for three hours. The yellow oil obtained by evaporating the solvent under reduced pressure was dissolved in chloroform (10 mL). To this solution, 2,5-difluorophenetole (3.4 g, 0.0214 mol) was added and then aluminum chloride (2.9 g, 0.0214 mol) was added portion wise at −10° C. over five minutes. After the reaction mixture was stirred at 5° C. for two hours, an iced water was added. This was extracted with chloroform three times. After the combined organic layer was washed with 1M hydrochloric acid, water, brine, it was dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain (5-bromo-2-chlorophenyl)(4-ethoxy-2,5-difluorophenyl)methanone (5.59 g, 70%) as a colorless crystal. The yellow oil obtained by evaporating the solvent under reduced pressure was dissolved in chloroform (10 mL) After the reaction mixture was stirred at 5° C. for two hours This was extracted with chloroform three times After the combined organic layer was washed with 1M hydrochloric acid, water, brine, it was dried with anhydrous magnesium sulfate After the desiccant was filtered off the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=10:1)

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

Procedure: Oxalyl chloride (1.89 mL, 0.0220 mol) and N,N-dimethylformamide (0.03 mL) were added to 5-bromo-2-chlorobenzoic acid (5.0 g, 0.0212 mol) in chloroform (10 mL) and stirred for three hours. The yellow oil obtained by evaporating the solvent under reduced pressure was dissolved in chloroform (10 mL). To this solution, 2,5-difluorophenetole (3.4 g, 0.0214 mol) was added and then aluminum chloride (2.9 g, 0.0214 mol) was added portion wise at −10° C. over five minutes. After the reaction mixture was stirred at 5° C. for two hours, an iced water was added. This was extracted with chloroform three times. After the combined organic layer was washed with 1M hydrochloric acid, water, brine, it was dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain (5-bromo-2-chlorophenyl)(4-ethoxy-2,5-difluorophenyl)methanone (5.59 g, 70%) as a colorless crystal. The yellow oil obtained by evaporating the solvent under reduced pressure was dissolved in chloroform (10 mL) After the reaction mixture was stirred at 5° C. for two hours This was extracted with chloroform three times After the combined organic layer was washed with 1M hydrochloric acid, water, brine, it was dried with anhydrous magnesium sulfate After the desiccant was filtered off the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=10:1)

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

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

Procedure: Oxalyl chloride (1.89 mL, 0.0220 mol) and N,N-dimethylformamide (0.03 mL) were added to 5-bromo-2-chlorobenzoic acid (5.0 g, 0.0212 mol) in chloroform (10 mL) and stirred for three hours. The yellow oil obtained by evaporating the solvent under reduced pressure was dissolved in chloroform (10 mL). To this solution, 2,5-difluorophenetole (3.4 g, 0.0214 mol) was added and then aluminum chloride (2.9 g, 0.0214 mol) was added portion wise at −10° C. over five minutes. After the reaction mixture was stirred at 5° C. for two hours, an iced water was added. This was extracted with chloroform three times. After the combined organic layer was washed with 1M hydrochloric acid, water, brine, it was dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain (5-bromo-2-chlorophenyl)(4-ethoxy-2,5-difluorophenyl)methanone (5.59 g, 70%) as a colorless crystal. The yellow oil obtained by evaporating the solvent under reduced pressure was dissolved in chloroform (10 mL) After the reaction mixture was stirred at 5° C. for two hours This was extracted with chloroform three times After the combined organic layer was washed with 1M hydrochloric acid, water, brine, it was dried with anhydrous magnesium sulfate After the desiccant was filtered off the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=10:1)

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

Procedure: Oxalyl chloride (1.89 mL, 0.0220 mol) and N,N-dimethylformamide (0.03 mL) were added to 5-bromo-2-chlorobenzoic acid (5.0 g, 0.0212 mol) in chloroform (10 mL) and stirred for three hours. The yellow oil obtained by evaporating the solvent under reduced pressure was dissolved in chloroform (10 mL). To this solution, 2,5-difluorophenetole (3.4 g, 0.0214 mol) was added and then aluminum chloride (2.9 g, 0.0214 mol) was added portion wise at −10° C. over five minutes. After the reaction mixture was stirred at 5° C. for two hours, an iced water was added. This was extracted with chloroform three times. After the combined organic layer was washed with 1M hydrochloric acid, water, brine, it was dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain (5-bromo-2-chlorophenyl)(4-ethoxy-2,5-difluorophenyl)methanone (5.59 g, 70%) as a colorless crystal. The yellow oil obtained by evaporating the solvent under reduced pressure was dissolved in chloroform (10 mL) After the reaction mixture was stirred at 5° C. for two hours This was extracted with chloroform three times After the combined organic layer was washed with 1M hydrochloric acid, water, brine, it was dried with anhydrous magnesium sulfate After the desiccant was filtered off the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=10:1)