5-bromo-2-phenylmethoxybenzaldehyde

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

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

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

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

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

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

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzyl bromide (18 mL, 14.9 mmol) and cesium carbonate (8.1 g, 24.9 mmol) were added to a solution of 2-hydroxy-5-bromo benzaldehyde 2 g, 9.95 mmol) in anhydrous DMF (25 mL) at room temperature. The reaction was heated to 80° C. for two hours, cooled and diluted with water (50 mL). The mixture was extracted with ethyl acetate (3×40 mL) and the combined organic layers were washed with water (1×50 mL) and brine (1×50 mL), dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (10% ethyl acetate/hexane) to afford 2.67 g of the title compound as a colorless oil (92%). MS: 291 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 7.94 (s, 1H); 7.6 (dd, 1H, J=8.9, 2.7 Hz); 7.39 (m, 6H); 6.92 (d, 1H, J=8.9 Hz); 5.18 (s, 2H). cooled The mixture was extracted with ethyl acetate (3×40 mL) the combined organic layers were washed with water (1×50 mL) and brine (1×50 mL) dried (Na2SO4) filtered concentrated The residue was purified by flash chromatography (10% ethyl acetate/hexane)

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

Procedure: Sodium borohydride (339 mg, 8.93 mmol) was added to a solution of 2-benzyloxy-5-bromo-benzaldehyde (2.6 g, 8.93 mmol) in anhydrous ethanol (20 mL) at 0° C. The reaction was allowed to warm to room temperature and, after 3 hours, the mixture was concentrated and the residue was dissolved in ethyl acetate (50 mL) and washed with water (1×25 mL), 1N HCl solution (1×25 mL) and brine (1×25 mL). The solution was dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (8% ethyl acetate/hexane) to afford 2.58 g of the title compound as a colorless oil (98%). the mixture was concentrated the residue was dissolved in ethyl acetate (50 mL) washed with water (1×25 mL), 1N HCl solution (1×25 mL) and brine (1×25 mL) The solution was dried (Na2SO4) filtered concentrated The residue was purified by flash chromatography (8% ethyl acetate/hexane)

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

Procedure: 2-Benzyloxy-5-bromobenzaldehyde and ethyl 4-aminomethylbenzoate were heated together at 100° C. for 1 hour. The mixture was cooled, dissolved in ethanol (100 ml) and sodium borohydride (1.3 g) was added. The mixture was stirred for 18 hours at ambient temperature, acidified with acetic acid and water (200 ml) was added. The mixture was extracted with diethyl ether (4×100 ml), the extracts washed with saturated aqueous NaHCO3, dried (MgSO4), filtered and evaporated to give ethyl 4-[N-(2-benzyloxy-5-bromobenzyl)aminomethyl]benzoate which was purified by chromatography on silica gel eluting with CH2Cl2 then 5% ethyl acetate/CH2Cl2 (yield 11.4 g). The mixture was cooled was added The mixture was extracted with diethyl ether (4×100 ml) the extracts washed with saturated aqueous NaHCO3 dried (MgSO4) filtered evaporated

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: 2-Benzyloxy-5-bromobenzaldehyde and ethyl 4-aminomethylbenzoate were heated together at 100° C. for 1 hour. The mixture was cooled, dissolved in ethanol (100 ml) and sodium borohydride (1.3 g) was added. The mixture was stirred for 18 hours at ambient temperature, acidified with acetic acid and water (200 ml) was added. The mixture was extracted with diethyl ether (4×100 ml), the extracts washed with saturated aqueous NaHCO3, dried (MgSO4), filtered and evaporated to give ethyl 4-[N-(2-benzyloxy-5-bromobenzyl)aminomethyl]benzoate which was purified by chromatography on silica gel eluting with CH2Cl2 then 5% ethyl acetate/CH2Cl2 (yield 11.4 g). The mixture was cooled was added The mixture was extracted with diethyl ether (4×100 ml) the extracts washed with saturated aqueous NaHCO3 dried (MgSO4) filtered evaporated