2-chloro-1-ethoxy-3-fluorobenzene

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: 606 g of the compound (b43) was added to a reactor in a nitrogen atmosphere, to which 570 g of bromine was added dropwise over 1 hour in a temperature range of 20 to 40° C., followed by stirring for 30 minutes. The resulting reaction mixture was washed with a saturated sodium thiosulfate aqueous solution, a 10% sodium hydroxide aqueous solution, and water. The resulting reaction mixture having been washed was subjected to fractional distillation under reduced pressure to obtain 760 g of 1-bromo-3-chloro-4-ethoxy-2-fluorobenzene (C2). The resulting compound (C2) was white solid and had a melting point of 65.4 to 66.1° C. and a boiling point of 125 to 127° C./8 mmHg. was added dropwise over 1 hour in a temperature range of 20 to 40° C. The resulting reaction mixture was washed with a saturated sodium thiosulfate aqueous solution The resulting reaction mixture having been washed was subjected to fractional distillation under reduced pressure

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

Procedure: 606 g of the compound (b43) was added to a reactor in a nitrogen atmosphere, to which 570 g of bromine was added dropwise over 1 hour in a temperature range of 20 to 40° C., followed by stirring for 30 minutes. The resulting reaction mixture was washed with a saturated sodium thiosulfate aqueous solution, a 10% sodium hydroxide aqueous solution, and water. The resulting reaction mixture having been washed was subjected to fractional distillation under reduced pressure to obtain 760 g of 1-bromo-3-chloro-4-ethoxy-2-fluorobenzene (C2). The resulting compound (C2) was white solid and had a melting point of 65.4 to 66.1° C. and a boiling point of 125 to 127° C./8 mmHg. was added dropwise over 1 hour in a temperature range of 20 to 40° C. The resulting reaction mixture was washed with a saturated sodium thiosulfate aqueous solution The resulting reaction mixture having been washed was subjected to fractional distillation under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 560 g of potassium hydroxide and 23 g of tetramethylammonium chloride (TMAC) were added to a reactor having 2,000 mL of ethanol placed therein in a temperature range of 50 to 60° C., followed by stirring for 30 minutes in that temperature range. Thereafter, the solution was heated to 80° C., and 594 g of a compound (b2) was added thereto over 1 hour in a temperature range of 80 to 85° C., followed by stirring for 5 hours at 80° C. After cooling the resulting reaction mixture to 25° C., 1,000 mL of toluene and 500 mL of water were added thereto and well mixed, and the mixture was left at rest to separate into an organic layer and an aqueous layer. After collecting the resulting organic layer, 500 mL of toluene was newly added to the aqueous mixture and well mixed, and the mixture was subjected to the same operation to extract again the compound contained in the aqueous layer. The toluene solution was added to the organic layer. After washing the organic layer with water in three times, the resulting organic layer was distilled under reduced pressure to obtain 606 g of 2-chloro-1-ethoxy-3-fluorobenzene (b43). The resulting liquid was colorless and had a boiling point of 98 to 99° C./8 mmHg. in a temperature range of 50 to 60° C. over 1 hour in a temperature range of 80 to 85° C. by stirring for 5 hours at 80° C After cooling the resulting reaction mixture to 25° C. well mixed the mixture was left at rest to separate into an organic layer After collecting the resulting organic layer, 500 mL of toluene was newly added to the aqueous mixture well mixed to extract again the compound The toluene solution was added to the organic layer After washing the organic layer with water in three times the resulting organic layer was distilled under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 560 g of potassium hydroxide and 23 g of tetramethylammonium chloride (TMAC) were added to a reactor having 2,000 mL of ethanol placed therein in a temperature range of 50 to 60° C., followed by stirring for 30 minutes in that temperature range. Thereafter, the solution was heated to 80° C., and 594 g of a compound (b2) was added thereto over 1 hour in a temperature range of 80 to 85° C., followed by stirring for 5 hours at 80° C. After cooling the resulting reaction mixture to 25° C., 1,000 mL of toluene and 500 mL of water were added thereto and well mixed, and the mixture was left at rest to separate into an organic layer and an aqueous layer. After collecting the resulting organic layer, 500 mL of toluene was newly added to the aqueous mixture and well mixed, and the mixture was subjected to the same operation to extract again the compound contained in the aqueous layer. The toluene solution was added to the organic layer. After washing the organic layer with water in three times, the resulting organic layer was distilled under reduced pressure to obtain 606 g of 2-chloro-1-ethoxy-3-fluorobenzene (b43). The resulting liquid was colorless and had a boiling point of 98 to 99° C./8 mmHg. in a temperature range of 50 to 60° C. over 1 hour in a temperature range of 80 to 85° C. by stirring for 5 hours at 80° C After cooling the resulting reaction mixture to 25° C. well mixed the mixture was left at rest to separate into an organic layer After collecting the resulting organic layer, 500 mL of toluene was newly added to the aqueous mixture well mixed to extract again the compound The toluene solution was added to the organic layer After washing the organic layer with water in three times the resulting organic layer was distilled under reduced pressure

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

Procedure: 606 g of the compound (b43) was added to a reactor in a nitrogen atmosphere, to which 570 g of bromine was added dropwise over 1 hour in a temperature range of 20 to 40° C., followed by stirring for 30 minutes. The resulting reaction mixture was washed with a saturated sodium thiosulfate aqueous solution, a 10% sodium hydroxide aqueous solution, and water. The resulting reaction mixture having been washed was subjected to fractional distillation under reduced pressure to obtain 760 g of 1-bromo-3-chloro-4-ethoxy-2-fluorobenzene (C2). The resulting compound (C2) was white solid and had a melting point of 65.4 to 66.1° C. and a boiling point of 125 to 127° C./8 mmHg. was added dropwise over 1 hour in a temperature range of 20 to 40° C. The resulting reaction mixture was washed with a saturated sodium thiosulfate aqueous solution The resulting reaction mixture having been washed was subjected to fractional distillation under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 560 g of potassium hydroxide and 23 g of tetramethylammonium chloride (TMAC) were added to a reactor having 2,000 mL of ethanol placed therein in a temperature range of 50 to 60° C., followed by stirring for 30 minutes in that temperature range. Thereafter, the solution was heated to 80° C., and 594 g of a compound (b2) was added thereto over 1 hour in a temperature range of 80 to 85° C., followed by stirring for 5 hours at 80° C. After cooling the resulting reaction mixture to 25° C., 1,000 mL of toluene and 500 mL of water were added thereto and well mixed, and the mixture was left at rest to separate into an organic layer and an aqueous layer. After collecting the resulting organic layer, 500 mL of toluene was newly added to the aqueous mixture and well mixed, and the mixture was subjected to the same operation to extract again the compound contained in the aqueous layer. The toluene solution was added to the organic layer. After washing the organic layer with water in three times, the resulting organic layer was distilled under reduced pressure to obtain 606 g of 2-chloro-1-ethoxy-3-fluorobenzene (b43). The resulting liquid was colorless and had a boiling point of 98 to 99° C./8 mmHg. in a temperature range of 50 to 60° C. over 1 hour in a temperature range of 80 to 85° C. by stirring for 5 hours at 80° C After cooling the resulting reaction mixture to 25° C. well mixed the mixture was left at rest to separate into an organic layer After collecting the resulting organic layer, 500 mL of toluene was newly added to the aqueous mixture well mixed to extract again the compound The toluene solution was added to the organic layer After washing the organic layer with water in three times the resulting organic layer was distilled under reduced pressure