ethyl 4-(aminomethyl)benzoate

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:; 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:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-aminomethylbenzoic acid (25 g) and concentrated sulphuric acid (25 ml) in ethanol (250 ml) was heated at reflux for 18 hours. The volume of solvent was reduced to a third by evaporation. The residue was poured onto ice (500 g) and basified with concentrated aqueous ammonia. The product was extracted with ethyl acetate (3×200 ml) and the extracts dried and evaporated to give ethyl 4-aminomethylbenzoate. was heated at reflux for 18 hours The volume of solvent was reduced to a third by evaporation The residue was poured onto ice (500 g) The product was extracted with ethyl acetate (3×200 ml) the extracts dried evaporated

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:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-aminomethylbenzoic acid (25 g) and concentrated sulphuric acid (25 ml) in ethanol (250 ml) was heated at reflux for 18 hours. The volume of solvent was reduced to a third by evaporation. The residue poured onto ice (500 g) and basified with concentrated aqueous ammonia. The product was extracted with ethyl acetate (3×200 ml) and the extracts dried and evaporated to give ethyl 4-aminomethylbenzoate. was heated at reflux for 18 hours The volume of solvent was reduced to a third by evaporation The residue poured onto ice (500 g) The product was extracted with ethyl acetate (3×200 ml) the extracts dried evaporated

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

Procedure: 3 g (19.9 mmol) of 4-aminomethylbenzoic acid was suspended in 100 ml of ethanol. 10 ml of ethanol containing 25% of hydrogen chloride was added to the suspension, and they were heated under reflux for 8 hours. The solvent was evaporated, and the title compound was obtained by the same isolation process as that of step 1 in Example 1 with ethyl acetate as the extractant. were heated under reflux for 8 hours The solvent was evaporated

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

Procedure: 3 g (19.9 mmol) of 4-aminomethylbenzoic acid was suspended in 100 ml of ethanol. 10 ml of ethanol containing 25% of hydrogen chloride was added to the suspension, and they were heated under reflux for 8 hours. The solvent was evaporated, and the title compound was obtained by the same isolation process as that of step 1 in Example 1 with ethyl acetate as the extractant. were heated under reflux for 8 hours The solvent was evaporated

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

Procedure: To a solution of 3-(3,4,5-trimethoxyphenyl)-2-(4-fluorophenyl)acrylic acid (0.6 g, 18 mmol) in DMF (5 mL) was added ethyl-4-aminomethylbenzoate.HCl (0.375 g, 21.6 mmol), EDCI (0.69 g, 36 mmol) and HOBt (0.24 g, 18 mmol). TEA (0.75 mL, 36 mmol) was added dropwise with constant stirring to the above reaction mixture and stirred overnight at room temperature. Subsequently the reaction mixture was evaporated to dryness, the residue was dissolved in ethyl acetate and washed successively with 1N HCl (3×50 mL), saturated NaHCO3 (3×50 mL) and brine solution (3×50 mL). The organic layer was dried over Na2SO4 and concentrated to give the pure compound (0.4 g, 50% yield). stirred overnight at room temperature Subsequently the reaction mixture was evaporated to dryness the residue was dissolved in ethyl acetate washed successively with 1N HCl (3×50 mL), saturated NaHCO3 (3×50 mL) and brine solution (3×50 mL) The organic layer was dried over Na2SO4 concentrated

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

Procedure: To a solution of 3-(3,4,5-trimethoxyphenyl)-2-(4-fluorophenyl)acrylic acid (0.6 g, 18 mmol) in DMF (5 mL) was added ethyl-4-aminomethylbenzoate.HCl (0.375 g, 21.6 mmol), EDCI (0.69 g, 36 mmol) and HOBt (0.24 g, 18 mmol). TEA (0.75 mL, 36 mmol) was added dropwise with constant stirring to the above reaction mixture and stirred overnight at room temperature. Subsequently the reaction mixture was evaporated to dryness, the residue was dissolved in ethyl acetate and washed successively with 1N HCl (3×50 mL), saturated NaHCO3 (3×50 mL) and brine solution (3×50 mL). The organic layer was dried over Na2SO4 and concentrated to give the pure compound (0.4 g, 50% yield). stirred overnight at room temperature Subsequently the reaction mixture was evaporated to dryness the residue was dissolved in ethyl acetate washed successively with 1N HCl (3×50 mL), saturated NaHCO3 (3×50 mL) and brine solution (3×50 mL) The organic layer was dried over Na2SO4 concentrated

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:; 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:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared from 3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]benzaldehyde and 4-aminomethyl-benzoic acid ethyl ester according to the procedure of Example 66. MS m/z 541; MS m/z 539.