1-Bromo-2-chloro-4-ethoxy-3-fluorobenzene

Conditions: temp:43.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.0 g of well dried magnesium and 30 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 43° C. 10.0 g of 1-bromo-2-chloro-4-ethoxy-3-fluorobenzene (6) dissolved in 20 mL of THF was slowly added dropwise thereto at a temperature range of from 43 to 51° C., followed by stirring for 30 minutes. Thereafter, 21.2 g of 4-(2-(trans-4-propylcyclohexyl)ethyl)cyclohexanone (7) dissolved in 20 mL of THF was slowly added dropwise thereto at a temperature range of from 50 to 55° C., followed by stirring for 30 minutes. After cooling the resulting reaction mixture to 25° C., the reaction mixture was mixed with 100 mL of 3N hydrochloric acid and 100 mL of toluene in a vessel and separated into an organic layer and an aqueous layer by standing still, so as to attain extraction to the organic layer. The resulting organic layer was fractionated and washed with water, a 2N sodium hydroxide aqueous solution, a saturated sodium bicarbonate aqueous solution and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was removed by distillation under reduced pressure to obtain 16.4 g of 1-(2-chloro-4-ethoxy-3-fluorophenyl)-4-(2-(trans-4-propylcyclohexyl)ethyl)cyclohexanol (8). The resulting compound (8) was a yellow solid matter. was slowly added dropwise of from 43 to 51° C. was slowly added dropwise of from 50 to 55° C. by stirring for 30 minutes After cooling the resulting reaction mixture to 25° C. separated into an organic layer extraction to the organic layer washed with water by drying over anhydrous magnesium sulfate Thereafter, the solvent was removed by distillation under reduced pressure

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

Procedure: 504 g of the compound (b44) was added to a reactor in a nitrogen atmosphere, to which 434 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 residue was subjected to fractional distillation under reduced pressure to obtain 605 g of 1-bromo-2-chloro-4-ethoxy-3-fluorobenzene (C12). The resulting compound (C12) was white solid and had a melting point of 48.0 to 48.5° C. and a boiling point of 88 to 90° C./1 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 residue was subjected to fractional distillation under reduced pressure

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

Procedure: 504 g of the compound (b44) was added to a reactor in a nitrogen atmosphere, to which 434 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 residue was subjected to fractional distillation under reduced pressure to obtain 605 g of 1-bromo-2-chloro-4-ethoxy-3-fluorobenzene (C12). The resulting compound (C12) was white solid and had a melting point of 48.0 to 48.5° C. and a boiling point of 88 to 90° C./1 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 residue was subjected to fractional distillation under reduced pressure

Conditions: temp:43.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1.0 g of well dried magnesium and 30 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 43° C. 10.0 g of 1-bromo-2-chloro-4-ethoxy-3-fluorobenzene (6) dissolved in 20 mL of THF was slowly added dropwise thereto at a temperature range of from 43 to 51° C., followed by stirring for 30 minutes. Thereafter, 21.2 g of 4-(2-(trans-4-propylcyclohexyl)ethyl)cyclohexanone (7) dissolved in 20 mL of THF was slowly added dropwise thereto at a temperature range of from 50 to 55° C., followed by stirring for 30 minutes. After cooling the resulting reaction mixture to 25° C., the reaction mixture was mixed with 100 mL of 3N hydrochloric acid and 100 mL of toluene in a vessel and separated into an organic layer and an aqueous layer by standing still, so as to attain extraction to the organic layer. The resulting organic layer was fractionated and washed with water, a 2N sodium hydroxide aqueous solution, a saturated sodium bicarbonate aqueous solution and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was removed by distillation under reduced pressure to obtain 16.4 g of 1-(2-chloro-4-ethoxy-3-fluorophenyl)-4-(2-(trans-4-propylcyclohexyl)ethyl)cyclohexanol (8). The resulting compound (8) was a yellow solid matter. was slowly added dropwise of from 43 to 51° C. was slowly added dropwise of from 50 to 55° C. by stirring for 30 minutes After cooling the resulting reaction mixture to 25° C. separated into an organic layer extraction to the organic layer washed with water by drying over anhydrous magnesium sulfate Thereafter, the solvent was removed by distillation under reduced pressure