1-(Benzyloxy)-4-bromo-2-(trifluoromethyl)benzene

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: Then, 5.10 g of 4-bromo-2-trifluoromethyl-1-benzyloxybenzene, 2.34 g of p-ethoxyphenol, 2.13 g of potassium carbonate, 100 mg of copper and 200 mg of cuprous chloride were charged into a reaction vessel, and stirred at 130° C. to 140° C. for 5 hours. The reaction solution was cooled to room temperature, poured into ice-water and then acidified by adding 10% hydrochloric acid. The solution was extracted twice with 100 ml of diethyl ether. Then, the ether layers were combined, washed with water, dried over anhydrous magnesium sulfate and concentrated to give a crude product. This crude product was subjected to silica gel chromatography to give 2.50 g of 2-trifluoromethyl-4-(4-ethoxyphenoxy)-1-benzyloxybenzene (yield, 41%). The solution was extracted twice with 100 ml of diethyl ether washed with water dried over anhydrous magnesium sulfate concentrated to give a crude product

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

Procedure: Then, 5.10 g of 4-bromo-2-trifluoromethyl-1-benzyloxybenzene, 2.34 g of p-ethoxyphenol, 2.13 g of potassium carbonate, 100 mg of copper and 200 mg of cuprous chloride were charged into a reaction vessel, and stirred at 130° C. to 140° C. for 5 hours. The reaction solution was cooled to room temperature, poured into ice-water and then acidified by adding 10% hydrochloric acid. The solution was extracted twice with 100 ml of diethyl ether. Then, the ether layers were combined, washed with water, dried over anhydrous magnesium sulfate and concentrated to give a crude product. This crude product was subjected to silica gel chromatography to give 2.50 g of 2-trifluoromethyl-4-(4-ethoxyphenoxy)-1-benzyloxybenzene (yield, 41%). The solution was extracted twice with 100 ml of diethyl ether washed with water dried over anhydrous magnesium sulfate concentrated to give a crude product

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

Procedure: Then, 8.47 g of 4-bromo-2-trifluoromethylphenol, 5.34 g of potassium carbonate, 4.49 g of benzyl chloride and 100 ml of N,N-dimethylformamide were charged into a reaction vessel, and stirred under ice cooling. After 24 hours, the reaction solution was poured into ice-water and extracted three times with 50 ml of diethyl ether. The ether layers were combined, washed with an aqueous 10 % sodium hydroxide solution, dried over anhydrous magnesium sulfate and then concentrated to give a crude product. This crude product was subjected to silica gel chromatography to give 9.38 g of 4-bromo-2-trifluoromethyl-1-benzyloxybenzene (yield, 81%). extracted three times with 50 ml of diethyl ether washed with an aqueous 10 % sodium hydroxide solution dried over anhydrous magnesium sulfate concentrated to give a crude product

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

Procedure: Then, 8.47 g of 4-bromo-2-trifluoromethylphenol, 5.34 g of potassium carbonate, 4.49 g of benzyl chloride and 100 ml of N,N-dimethylformamide were charged into a reaction vessel, and stirred under ice cooling. After 24 hours, the reaction solution was poured into ice-water and extracted three times with 50 ml of diethyl ether. The ether layers were combined, washed with an aqueous 10 % sodium hydroxide solution, dried over anhydrous magnesium sulfate and then concentrated to give a crude product. This crude product was subjected to silica gel chromatography to give 9.38 g of 4-bromo-2-trifluoromethyl-1-benzyloxybenzene (yield, 81%). extracted three times with 50 ml of diethyl ether washed with an aqueous 10 % sodium hydroxide solution dried over anhydrous magnesium sulfate concentrated to give a crude product

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

Procedure: Then, 5.10 g of 4-bromo-2-trifluoromethyl-1-benzyloxybenzene, 2.34 g of p-ethoxyphenol, 2.13 g of potassium carbonate, 100 mg of copper and 200 mg of cuprous chloride were charged into a reaction vessel, and stirred at 130° C. to 140° C. for 5 hours. The reaction solution was cooled to room temperature, poured into ice-water and then acidified by adding 10% hydrochloric acid. The solution was extracted twice with 100 ml of diethyl ether. Then, the ether layers were combined, washed with water, dried over anhydrous magnesium sulfate and concentrated to give a crude product. This crude product was subjected to silica gel chromatography to give 2.50 g of 2-trifluoromethyl-4-(4-ethoxyphenoxy)-1-benzyloxybenzene (yield, 41%). The solution was extracted twice with 100 ml of diethyl ether washed with water dried over anhydrous magnesium sulfate concentrated to give a crude product

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

Procedure: Then, 8.47 g of 4-bromo-2-trifluoromethylphenol, 5.34 g of potassium carbonate, 4.49 g of benzyl chloride and 100 ml of N,N-dimethylformamide were charged into a reaction vessel, and stirred under ice cooling. After 24 hours, the reaction solution was poured into ice-water and extracted three times with 50 ml of diethyl ether. The ether layers were combined, washed with an aqueous 10 % sodium hydroxide solution, dried over anhydrous magnesium sulfate and then concentrated to give a crude product. This crude product was subjected to silica gel chromatography to give 9.38 g of 4-bromo-2-trifluoromethyl-1-benzyloxybenzene (yield, 81%). extracted three times with 50 ml of diethyl ether washed with an aqueous 10 % sodium hydroxide solution dried over anhydrous magnesium sulfate concentrated to give a crude product

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

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

Procedure: Then, 5.10 g of 4-bromo-2-trifluoromethyl-1-benzyloxybenzene, 2.34 g of p-ethoxyphenol, 2.13 g of potassium carbonate, 100 mg of copper and 200 mg of cuprous chloride were charged into a reaction vessel, and stirred at 130° C. to 140° C. for 5 hours. The reaction solution was cooled to room temperature, poured into ice-water and then acidified by adding 10% hydrochloric acid. The solution was extracted twice with 100 ml of diethyl ether. Then, the ether layers were combined, washed with water, dried over anhydrous magnesium sulfate and concentrated to give a crude product. This crude product was subjected to silica gel chromatography to give 2.50 g of 2-trifluoromethyl-4-(4-ethoxyphenoxy)-1-benzyloxybenzene, (yield, 41%). The solution was extracted twice with 100 ml of diethyl ether washed with water dried over anhydrous magnesium sulfate concentrated to give a crude product to give

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

Procedure: Then, 8.47 g of 4-bromo-2-trifluoromethylphenol, 5.34 g of potassium carbonate, 4.49 g of benzyl chloride and 100 ml of N,N-dimethylformamide were charged into a reaction vessel, and stirred under ice cooling. After 24 hours, the reaction solution was poured into ice-water and extracted three times with 50 ml of diethyl ether. The ether layers were combined, washed with an aqueous 10 % sodium hydroxide solution, dried over anhydrous magnesium sulfate and then concentrated to give a crude product. This crude product was subjected to silica gel chromatography to give 9.38 g of 4-bromo-2-trifluoromethyl-1-benzyloxybenzene, (yield, 81%). extracted three times with 50 ml of diethyl ether washed with an aqueous 10 % sodium hydroxide solution dried over anhydrous magnesium sulfate concentrated to give a crude product to give

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

Procedure: To a solution of 4-bromo-2-(trifluoromethyl)phenol (4.37 g) in N,N-dimethylformamide (40 ml) were added potassium carbonate (3.75 g) and benzyl bromide (2.59 ml), and the mixture was stirred for 12 hours at room temperature. To the reaction mixture was added water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. After the solvent was removed under reduced pressure, purification of the residue by flash column chromatography on silica gel (eluent: hexane/ethyl acetate=10/1) gave benzyl 4-bromo-2-(trifluoromethyl)phenyl ether (3.37 g). To a stirred solution of the obtained benzyl 4-bromo-2-(trifluoromethyl)phenyl ether (2.05 g) in diethyl ether (20 ml) was added 1.46M tert-butyl lithium solution in pentane (11.4 ml) at −100° C., and the mixture was stirred for 5 minutes. An excess amount of ethylene oxide was added to the reaction mixture, and the mixture was gradually allowed to warm up to −50° C. After a saturated aqueous ammonium chloride solution was added to the reaction mixture, the resulting mixture was allowed to warm up to room temperature and extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate. After the solvent was removed under reduced pressure, purification of the residue by flash column chromatography on silica gel (eluent: hexane/ethyl acetate=2/1) gave 4′-benzyloxy-3′-(trifluoromethyl)phenethyl alcohol (1.46 g). the resulting mixture was extracted with ethyl acetate The extract was washed with water dried over anhydrous magnesium sulfate After the solvent was removed under reduced pressure, purification of the residue by flash column chromatography on silica gel (eluent: hexane/ethyl acetate=10/1)