2-bromo-4-methyl-1-phenylmethoxybenzene

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

Procedure: To a solution of 2-bromo-4-methylphenol (1.5 g, 8.0 mmol) in N,N-dimethylformamide (40 mL), potassium carbonate (1.32 g, 9.6 mmol) was added and furthermore benzyl bromide (1.05 mL, 8.8 mmol) was added thereto. The mixture solution was stirred at room temperature for 12 hours, and then water was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried (anhydrous magnesium sulfate), and then the solvent was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:4)] to obtain the title compound (1.72 g, 77%). the mixture was extracted with ethyl acetate The organic layer was washed with a saturated sodium chloride aqueous solution dried (anhydrous magnesium sulfate) the solvent was distilled under reduced pressure The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:4)]

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100.0 g (2.56 mol) of sodium amide was added to 700 g (6.53 mol) of benzylamine under an argon atmosphere, and the mixture was stirred for 10 minutes at 60° C. A solution of 222.20 g (0.801 mol) of 1-benzyloxy-2-bromo-4-methylbenzene was dissolved in 400 ml of tetrahydrofuran was added dropwise to the above mixture over 50 minutes. The mixture was stirred for 50 minutes while maintaining the temperature at 60° C. Methanol was added under cooling with ice, and the mixture was poured into ice water. The reaction mixture was extracted with ethyl acetate-water, and the organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The residue obtained by evaporating the solvent was purified by column chromatography (silica gel, 10:1 mixture of n-hexane and ethyl acetate). The crude product thus obtained was recrystallized from n-hexane to obtain 175.80 g (yield: 72.3%) of the title compound as colorless needles. was added dropwise to the above mixture over 50 minutes The mixture was stirred for 50 minutes while maintaining the temperature at 60° C under cooling with ice The reaction mixture was extracted with ethyl acetate-water the organic layer was washed with saturated brine dried over anhydrous sodium sulfate The residue obtained by evaporating the solvent was purified by column chromatography (silica gel, 10:1 mixture of n-hexane and ethyl acetate) The crude product thus obtained was recrystallized from n-hexane

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

Procedure: The title compound 5c was prepared according to the method for preparation of compound 3d of Example 3 by replacing 3c with 5b.

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

Procedure: To a solution of 1-(benzyloxy)-2-bromo-4-methylbenzene (3a) (1.0 g, 3.6 mmol) in THF (20 mL) at −78° C. under N2 atmosphere was added n-BuLi (2.5 M, 1.6 mL, 3.9 mmol), the resulting mixture was stirred for 30 min and (S)-2-methyloxirane (0.38 mL, 5.4 mmol) and BF3.Et2O (0.67 mL, 5.4 mmol) were added to the mixture. It was stirred at −78° C. for 1.5 h and warmed up to ambient temperature, quenched with water (10 mL), extracted with EtOAc (30 mL), washed with brine, dried and concentrated. The residue was purified by column chromatography on silica gel eluting with hexanes/EtOAc (10:1) to give the title compound (3b). It was stirred at −78° C. for 1.5 h quenched with water (10 mL) extracted with EtOAc (30 mL) washed with brine dried concentrated The residue was purified by column chromatography on silica gel eluting with hexanes/EtOAc (10:1)

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 2-bromo-4-methylphenol (5.0 g, 27 mmol) and K2CO3 (7.4 g, 53 mmol) in DMF (20 mL) was added benzyl bromide (3.5 mL, 29 mmol) at ambient temperature. It was stirred at 70° C., for 12 h. The mixture was poured into water (50 mL), extracted with EtOAc (150 mL), washed with water, brine, dried and concentrated. The residue was purified by column chromatography on silica gel eluting with hexanes/EtOAc (10:1) to give the title compound (3a). extracted with EtOAc (150 mL) washed with water, brine dried concentrated The residue was purified by column chromatography on silica gel eluting with hexanes/EtOAc (10:1)

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

Procedure: To a solution of 2-bromo-4-methylphenol (1.5 g, 8.0 mmol) in N,N-dimethylformamide (40 mL), potassium carbonate (1.32 g, 9.6 mmol) was added and furthermore benzyl bromide (1.05 mL, 8.8 mmol) was added thereto. The mixture solution was stirred at room temperature for 12 hours, and then water was added thereto and the mixture was extracted with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried (anhydrous magnesium sulfate), and then the solvent was distilled under reduced pressure. The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:4)] to obtain the title compound (1.72 g, 77%). the mixture was extracted with ethyl acetate The organic layer was washed with a saturated sodium chloride aqueous solution dried (anhydrous magnesium sulfate) the solvent was distilled under reduced pressure The obtained residue was purified by silica gel column chromatography [developing solution=ethyl acetate:n-hexane (1:4)]