1-bromo-4-(2-chloroethoxy)benzene

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

Procedure: Tert-Butoxypotassium (33.7 g, 300 mmol) was added to a solution of tetrahydrofuran (hereinafter THF) (250 mL) containing 1-bromo-4-(2-chloroethoxy)benzene (58.6 g, 249 mmol) prepared in Example 6 (6a) over 10 minutes at −10° C. The mixture was stirred at room temperature for 21 hours, and water (500 mL) was added thereto. The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice. The organic layers were combined, washed with saturated brine (100 mL) twice, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated. The resulting residue was dissolved in hexane (100 mL), and the precipitated insoluble substance was removed by filtration. The insoluble substance was further washed with hexane (5 mL) five times. The filtrates were combined, concentrated, and purified by silica gel column chromatography (hexane) to give 39.0 g of the title compound (colorless oil, yield: 79%). The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice washed with saturated brine (100 mL) twice dried over anhydrous magnesium sulfate Then, the solvent was evaporated The resulting residue was dissolved in hexane (100 mL) the precipitated insoluble substance was removed by filtration The insoluble substance was further washed with hexane (5 mL) five times concentrated purified by silica gel column chromatography (hexane)

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With reference to the document (J. Org. Chem., (2002), 67, 1093-1101), potassium carbonate (83.0 g, 600 mmol) was added to a solution of DMF (500 mL) containing 4-bromophenol (50.4 g, 291 mmol) at room temperature. The mixture was stirred at the same temperature for 30 minutes, and then 2-chloroethyl 4-methylbenzenesulfonate (70.2 g, 299 mmol) was added thereto. The mixture was stirred at 50° C. for 24 hours. The reaction solution was cooled to 10° C., and water (500 mL) was added thereto to precipitate a white solid. This white solid was collected by filtration, washed with water (500 mL), and dried at 50° C. under reduced pressure to give 58.6 g of the title compound (yield: 86%). The mixture was stirred at 50° C. for 24 hours to precipitate a white solid This white solid was collected by filtration washed with water (500 mL) dried at 50° C. under reduced pressure

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With reference to the document (J. Org. Chem., (2002), 67, 1093-1101), potassium carbonate (83.0 g, 600 mmol) was added to a solution of DMF (500 mL) containing 4-bromophenol (50.4 g, 291 mmol) at room temperature. The mixture was stirred at the same temperature for 30 minutes, and then 2-chloroethyl 4-methylbenzenesulfonate (70.2 g, 299 mmol) was added thereto. The mixture was stirred at 50° C. for 24 hours. The reaction solution was cooled to 10° C., and water (500 mL) was added thereto to precipitate a white solid. This white solid was collected by filtration, washed with water (500 mL), and dried at 50° C. under reduced pressure to give 58.6 g of the title compound (yield: 86%). The mixture was stirred at 50° C. for 24 hours to precipitate a white solid This white solid was collected by filtration washed with water (500 mL) dried at 50° C. under reduced pressure

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

Procedure: Tert-Butoxypotassium (33.7 g, 300 mmol) was added to a solution of tetrahydrofuran (hereinafter THF) (250 mL) containing 1-bromo-4-(2-chloroethoxy)benzene (58.6 g, 249 mmol) prepared in Example 6 (6a) over 10 minutes at −10° C. The mixture was stirred at room temperature for 21 hours, and water (500 mL) was added thereto. The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice. The organic layers were combined, washed with saturated brine (100 mL) twice, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated. The resulting residue was dissolved in hexane (100 mL), and the precipitated insoluble substance was removed by filtration. The insoluble substance was further washed with hexane (5 mL) five times. The filtrates were combined, concentrated, and purified by silica gel column chromatography (hexane) to give 39.0 g of the title compound (colorless oil, yield: 79%). The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice washed with saturated brine (100 mL) twice dried over anhydrous magnesium sulfate Then, the solvent was evaporated The resulting residue was dissolved in hexane (100 mL) the precipitated insoluble substance was removed by filtration The insoluble substance was further washed with hexane (5 mL) five times concentrated purified by silica gel column chromatography (hexane)

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With reference to the document (J. Org. Chem., (2002), 67, 1093-1101), potassium carbonate (83.0 g, 600 mmol) was added to a solution of DMF (500 mL) containing 4-bromophenol (50.4 g, 291 mmol) at room temperature. The mixture was stirred at the same temperature for 30 minutes, and then 2-chloroethyl 4-methylbenzenesulfonate (70.2 g, 299 mmol) was added thereto. The mixture was stirred at 50° C. for 24 hours. The reaction solution was cooled to 10° C., and water (500 mL) was added thereto to precipitate a white solid. This white solid was collected by filtration, washed with water (500 mL), and dried at 50° C. under reduced pressure to give 58.6 g of the title compound (yield: 86%). The mixture was stirred at 50° C. for 24 hours to precipitate a white solid This white solid was collected by filtration washed with water (500 mL) dried at 50° C. under reduced pressure

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With reference to the document (J. Org. Chem., (2002), 67, 1093-1101), potassium carbonate (83.0 g, 600 mmol) was added to a solution of DMF (500 mL) containing 4-bromophenol (50.4 g, 291 mmol) at room temperature. The mixture was stirred at the same temperature for 30 minutes, and then 2-chloroethyl 4-methylbenzenesulfonate (70.2 g, 299 mmol) was added thereto. The mixture was stirred at 50° C. for 24 hours. The reaction solution was cooled to 10° C., and water (500 mL) was added thereto to precipitate a white solid. This white solid was collected by filtration, washed with water (500 mL), and dried at 50° C. under reduced pressure to give 58.6 g of the title compound (yield: 86%). The mixture was stirred at 50° C. for 24 hours to precipitate a white solid This white solid was collected by filtration washed with water (500 mL) dried at 50° C. under reduced pressure

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

Procedure: To a THF (250 mL) solution of 1-bromo-4-(2-chloroethoxy)benzene (58.6 g, 249 mmol) prepared in Example 5 (5a) was added tert-butoxy potassium (33.7 g, 300 mmol) at −10° C. over 10 minutes. The resulting mixture was stirred at room temperature for 21 hours. Water (500 mL) was added thereto, and the mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice. The organic layers were combined, washed with saturated brine (100 mL) twice, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated. The resulting residue was dissolved in n-hexane (100 mL), and the precipitated insoluble substance was removed by filtration, and this insoluble substance was further washed with n-hexane (5 mL) five times. These filtrates were combined and concentrated, and then purified by silica gel column chromatography (n-hexane) to give 39.0 g of the title compound (colorless oil, yield: 79%). the mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice washed with saturated brine (100 mL) twice dried over anhydrous magnesium sulfate Then, the solvent was evaporated The resulting residue was dissolved in n-hexane (100 mL) the precipitated insoluble substance was removed by filtration this insoluble substance was further washed with n-hexane (5 mL) five times concentrated purified by silica gel column chromatography (n-hexane)

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The preparation was conducted according to the description in the document (J. Org. Chem., (2002), 67, 1093-1101). Potassium carbonate (83.0 g, 600 mmol) was added to an N,N-dimethylformamide (DMF, 500 mL) solution of 4-bromophenol (50.4 g, 291 mmol) at room temperature. The mixture was stirred at the same temperature for 30 minutes, and then 2-chloroethyl p-toluenesulfonate (70.2 g, 299 mmol) was added thereto. The resulting mixture was stirred at 50° C. for 24 hours. The reaction solution was cooled to 110° C., and water (500 mL) was added thereto to precipitate a white solid. The solid was collected by filtration, washed with water (500 mL), and dried under reduced pressure to give 58.6 g of the title compound (white powder, yield: 86%). The resulting mixture was stirred at 50° C. for 24 hours to precipitate a white solid The solid was collected by filtration washed with water (500 mL) dried under reduced pressure

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

Procedure: Tert-Butoxypotassium (33.7 g, 300 mmol) was added to a solution of tetrahydrofuran (hereinafter THF) (250 mL) containing 1-bromo-4-(2-chloroethoxy)benzene (58.6 g, 249 mmol) prepared in Example 6 (6a) over 10 minutes at −10° C. The mixture was stirred at room temperature for 21 hours, and water (500 mL) was added thereto. The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice. The organic layers were combined, washed with saturated brine (100 mL) twice, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated. The resulting residue was dissolved in hexane (100 mL), and the precipitated insoluble substance was removed by filtration. The insoluble substance was further washed with hexane (5 mL) five times. The filtrates were combined, concentrated, and purified by silica gel column chromatography (hexane) to give 39.0 g of the title compound (colorless oil, yield: 79%). The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice washed with saturated brine (100 mL) twice dried over anhydrous magnesium sulfate Then, the solvent was evaporated The resulting residue was dissolved in hexane (100 mL) the precipitated insoluble substance was removed by filtration The insoluble substance was further washed with hexane (5 mL) five times concentrated purified by silica gel column chromatography (hexane)

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With reference to the document (J. Org. Chem., (2002), 67, 1093-1101), potassium carbonate (83.0 g, 600 mmol) was added to a solution of DMF (500 mL) containing 4-bromophenol (50.4 g, 291 mmol) at room temperature. The mixture was stirred at the same temperature for 30 minutes, and then 2-chloroethyl 4-methylbenzenesulfonate (70.2 g, 299 mmol) was added thereto. The mixture was stirred at 50° C. for 24 hours. The reaction solution was cooled to 10° C., and water (500 mL) was added thereto to precipitate a white solid. This white solid was collected by filtration, washed with water (500 mL), and dried at 50° C. under reduced pressure to give 58.6 g of the title compound (yield: 86%). The mixture was stirred at 50° C. for 24 hours to precipitate a white solid This white solid was collected by filtration washed with water (500 mL) dried at 50° C. under reduced pressure

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

Procedure: Tert-Butoxypotassium (33.7 g, 300 mmol) was added to a solution of tetrahydrofuran (hereinafter THF) (250 mL) containing 1-bromo-4-(2-chloroethoxy)benzene (58.6 g, 249 mmol) prepared in Example 6 (6a) over 10 minutes at −10° C. The mixture was stirred at room temperature for 21 hours, and water (500 mL) was added thereto. The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice. The organic layers were combined, washed with saturated brine (100 mL) twice, and dried over anhydrous magnesium sulfate. Then, the solvent was evaporated. The resulting residue was dissolved in hexane (100 mL), and the precipitated insoluble substance was removed by filtration. The insoluble substance was further washed with hexane (5 mL) five times. The filtrates were combined, concentrated, and purified by silica gel column chromatography (hexane) to give 39.0 g of the title compound (colorless oil, yield: 79%). The resulting mixture was extracted with methyl tert-butyl ether (200 mL, 150 mL) twice washed with saturated brine (100 mL) twice dried over anhydrous magnesium sulfate Then, the solvent was evaporated The resulting residue was dissolved in hexane (100 mL) the precipitated insoluble substance was removed by filtration The insoluble substance was further washed with hexane (5 mL) five times concentrated purified by silica gel column chromatography (hexane)

Conditions: temp:10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: With reference to the document (J. Org. Chem., (2002), 67, 1093-1101), potassium carbonate (83.0 g, 600 mmol) was added to a solution of DMF (500 mL) containing 4-bromophenol (50.4 g, 291 mmol) at room temperature. The mixture was stirred at the same temperature for 30 minutes, and then 2-chloroethyl 4-methylbenzenesulfonate (70.2 g, 299 mmol) was added thereto. The mixture was stirred at 50° C. for 24 hours. The reaction solution was cooled to 10° C., and water (500 mL) was added thereto to precipitate a white solid. This white solid was collected by filtration, washed with water (500 mL), and dried at 50° C. under reduced pressure to give 58.6 g of the title compound (yield: 86%). The mixture was stirred at 50° C. for 24 hours to precipitate a white solid This white solid was collected by filtration washed with water (500 mL) dried at 50° C. under reduced pressure