3-bromo-4-phenylmethoxybenzaldehyde

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

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

Procedure: Then, 1.6 M n-butyllithium hexane solution (22.9 mL) was added to a mixture of 4-bromophenetole (7.3 g, 0.037 mol) and tetrahydrofuran (70 mL) at −78° C. After stirred for 0.5 hours, 4-benzyloxy-3-bromobenzaldehyde (7.0 g, 0.024 mol) in a tetrahydrofuran (70 mL) solution was added and further stirred for 15 minutes, and the reaction mixture was warmed to room temperature. After the reaction mixture was added with a saturated ammonium chloride aqueous solution and extracted with ethyl acetate, the organic phase was washed with brine and dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain colorless oily [4-(benzyloxy)-3-bromophenyl](4-ethoxyphenyl)methanol (8.7 g, 86%). further stirred for 15 minutes extracted with ethyl acetate the organic phase was washed with brine dried with anhydrous magnesium sulfate After the desiccant was filtered off the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)

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

Procedure: Benzyl bromide (3.1 mL, 0.026 mol) was added to a mixture of 3-bromo-4-hydroxybenzaldehyde (5.0 g, 0.025 mol), tetrabutylammonium iodide (0.92 g, 2.5 mmol), potassium carbonate (6.9 g, 0.050 mol) and N,N-dimethylformamide (70 mL) at room temperature and stirred for 2.5 hours. An ice-water mixture (100 mL) was poured to the reaction mixture and the resultant solution was stirred for one hour. A resulting precipitate was filtered and dried to obtain 4-benzyloxy-3-bromobenzaldehyde (7.1 g, 98%) as a pale yellow powder. A resulting precipitate was filtered dried

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

Procedure: Benzyl bromide (3.1 mL, 0.026 mol) was added to a mixture of 3-bromo-4-hydroxybenzaldehyde (5.0 g, 0.025 mol), tetrabutylammonium iodide (0.92 g, 2.5 mmol), potassium carbonate (6.9 g, 0.050 mol) and N,N-dimethylformamide (70 mL) at room temperature and stirred for 2.5 hours. An ice-water mixture (100 mL) was poured to the reaction mixture and the resultant solution was stirred for one hour. A resulting precipitate was filtered and dried to obtain 4-benzyloxy-3-bromobenzaldehyde (7.1 g, 98%) as a pale yellow powder. A resulting precipitate was filtered dried

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

Procedure: Then, 1.6 M n-butyllithium hexane solution (22.9 mL) was added to a mixture of 4-bromophenetole (7.3 g, 0.037 mol) and tetrahydrofuran (70 mL) at −78° C. After stirred for 0.5 hours, 4-benzyloxy-3-bromobenzaldehyde (7.0 g, 0.024 mol) in a tetrahydrofuran (70 mL) solution was added and further stirred for 15 minutes, and the reaction mixture was warmed to room temperature. After the reaction mixture was added with a saturated ammonium chloride aqueous solution and extracted with ethyl acetate, the organic phase was washed with brine and dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain colorless oily [4-(benzyloxy)-3-bromophenyl](4-ethoxyphenyl)methanol (8.7 g, 86%). further stirred for 15 minutes extracted with ethyl acetate the organic phase was washed with brine dried with anhydrous magnesium sulfate After the desiccant was filtered off the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)

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

Procedure: Benzyl bromide (3.1 mL, 0.026 mol) was added to a mixture of 3-bromo-4-hydroxybenzaldehyde (5.0 g, 0.025 mol), tetrabutylammonium iodide (0.92 g, 2.5 mmol), potassium carbonate (6.9 g, 0.050 mol) and N,N-dimethylformamide (70 mL) at room temperature and stirred for 2.5 hours. An ice-water mixture (100 mL) was poured to the reaction mixture and the resultant solution was stirred for one hour. A resulting precipitate was filtered and dried to obtain 4-benzyloxy-3-bromobenzaldehyde (7.1 g, 98%) as a pale yellow powder. A resulting precipitate was filtered dried

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

Procedure: 25 g (86 mmol) of 4-benzyloxy-3-bromo-benzaldehyde, 500 ml of methanol, 29 g (430 mmol) of methylamine hydrochloride and 8 g (127 mmol) of sodium cyanoborohydride are introduced into a round-bottomed flask under a stream of nitrogen. The reaction medium is stirred for 48 hours at room temperature. The methanol is evaporated off. The residue is taken up in ethyl acetate and water and then acidified. After separation of the phases once settling has taken place, the aqueous phase is returned to basic pH with sodium hydroxide and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate, filtered and then evaporated. The residue is purified by chromatography on a column of silica eluted with a dichloromethane/ethanol mixture (9/1). 9.9 g (38%) of the expected product are obtained in the form of a colorless oil. The methanol is evaporated off After separation of the phases extracted with ethyl acetate The organic phase is dried over magnesium sulfate filtered evaporated The residue is purified by chromatography on a column of silica eluted with a dichloromethane/ethanol mixture (9/1)

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

Procedure: 3-Bromo-4-hydroxy-benzaldehyde (1.9 g, 9.45 mmol) was added slowly, at 0° C., to a suspension of NaH 95% (290 mg, 11.34 nol) in dry N,N-dimethylformamide (45 mL). The mixture was stirred for 0.5 hours. Benzyl chloride (1.3 mL, 11.34 mmol) was added and the reaction stirred at room temperature overnight. 1N HCl (40 mL) was added and the layers separated. The aqueous layer was extracted with diethyl ether (5×50 mL) and the combined organic layers were dried (Na2SO4), filtered, and concentrated under vacuum. The residue was chromatographed (silica gel, hexanes/ethyl acetate 9:1) to produce 4-Benzyloxy-3-bromo-benzaldehyde as a white solid (2.47 g, 90%). 1H-NMR (CDCl3, 200.15 MHz): δ 9.82 (s, 1H), 8.09 (d, 1H, J=1.8), 7.76 (dd, 1H, J=8.4, 1.8), 7.47–7.32 (m, 5H), 7.02 (d, 1H, J=8.4), 5.24 (s, 2H. the reaction stirred at room temperature overnight the layers separated The aqueous layer was extracted with diethyl ether (5×50 mL) the combined organic layers were dried (Na2SO4) filtered concentrated under vacuum The residue was chromatographed (silica gel, hexanes/ethyl acetate 9:1)

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

Procedure: 3-Bromo-4-hydroxy-benzaldehyde (1.9 g, 9.45 mmol) was added slowly, at 0° C., to a suspension of NaH 95% (290 mg, 11.34 nol) in dry N,N-dimethylformamide (45 mL). The mixture was stirred for 0.5 hours. Benzyl chloride (1.3 mL, 11.34 mmol) was added and the reaction stirred at room temperature overnight. 1N HCl (40 mL) was added and the layers separated. The aqueous layer was extracted with diethyl ether (5×50 mL) and the combined organic layers were dried (Na2SO4), filtered, and concentrated under vacuum. The residue was chromatographed (silica gel, hexanes/ethyl acetate 9:1) to produce 4-Benzyloxy-3-bromo-benzaldehyde as a white solid (2.47 g, 90%). 1H-NMR (CDCl3, 200.15 MHz): δ 9.82 (s, 1H), 8.09 (d, 1H, J=1.8), 7.76 (dd, 1H, J=8.4, 1.8), 7.47–7.32 (m, 5H), 7.02 (d, 1H, J=8.4), 5.24 (s, 2H. the reaction stirred at room temperature overnight the layers separated The aqueous layer was extracted with diethyl ether (5×50 mL) the combined organic layers were dried (Na2SO4) filtered concentrated under vacuum The residue was chromatographed (silica gel, hexanes/ethyl acetate 9:1)

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

Procedure: 1.0 g (3.43 mmol) of 4-(benzyloxy)-3-bromobenzaldehyde [Lit.: R. Baker et al., J. Chem. Soc. Chem. Commun. 14, 1102-1104 (1987)] is initially charged in 10 ml of tetrahydrofuran. At 0° C., 0.04 g (1.03 mmol) of sodium borohydride is added. The reaction mixture is stirred at room temperature for 3 hours. Saturated ammonium chloride solution is then added, and the mixture is extracted twice with ethyl acetate. The combined organic phases are dried with sodium sulphate and the solvent is removed under reduced pressure. This gives 0.98 g (97% of theory) of [4-(benzyloxy)-3-bromophenyl]methanol. the mixture is extracted twice with ethyl acetate The combined organic phases are dried with sodium sulphate the solvent is removed under reduced pressure

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

Procedure: Then, 1.6 M n-butyllithium hexane solution (22.9 mL) was added to a mixture of 4-bromophenetole (7.3 g, 0.037 mol) and tetrahydrofuran (70 mL) at −78° C. After stirred for 0.5 hours, 4-benzyloxy-3-bromobenzaldehyde (7.0 g, 0.024 mol) in a tetrahydrofuran (70 mL) solution was added and further stirred for 15 minutes, and the reaction mixture was warmed to room temperature. After the reaction mixture was added with a saturated ammonium chloride aqueous solution and extracted with ethyl acetate, the organic phase was washed with brine and dried with anhydrous magnesium sulfate. After the desiccant was filtered off, the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to obtain colorless oily [4-(benzyloxy)-3-bromophenyl](4-ethoxyphenyl)methanol (8.7 g, 86%). further stirred for 15 minutes extracted with ethyl acetate the organic phase was washed with brine dried with anhydrous magnesium sulfate After the desiccant was filtered off the residue obtained by evaporating the solvent under reduced pressure was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)

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

Procedure: Benzyl bromide (3.1 mL, 0.026 mol) was added to a mixture of 3-bromo-4-hydroxybenzaldehyde (5.0 g, 0.025 mol), tetrabutylammonium iodide (0.92 g, 2.5 mmol), potassium carbonate (6.9 g, 0.050 mol) and N,N-dimethylformamide (70 mL) at room temperature and stirred for 2.5 hours. An ice-water mixture (100 mL) was poured to the reaction mixture and the resultant solution was stirred for one hour. A resulting precipitate was filtered and dried to obtain 4-benzyloxy-3-bromobenzaldehyde (7.1 g, 98%) as a pale yellow powder. A resulting precipitate was filtered dried