methyl 3-[4-(aminomethyl)phenyl]propanoate

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

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

Procedure: To a solution of 6-bromo-4-phenyl-3-isocoumarincarboxylic acid methyl ester (359 mg) in methanol (20 ml) was added 3-(4-aminomethylphenyl)propionic acid methyl ester (387 mg) and the mixture was stirred at room temperature for 18 hr. The solvent was evaporated under reduced pressure, 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried by adding sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was dissolved in methanol (30 ml) and conc. sulfuric acid (3 ml) was added. The mixture was heated under reflux for 3 hrs. The solvent was evaporated under reduced pressure, water was added under ice-cooling and the mixture was neutralized with potassium carbonate. The solution was extracted with ethyl acetate. The extract was washed with saturated brine and dried by adding sodium sulfate. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→3/1) to give the title compound (425 mg, 80%). The solvent was evaporated under reduced pressure, 1N hydrochloric acid was added the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried by adding sodium sulfate The solvent was evaporated under reduced pressure the obtained residue was dissolved in methanol (30 ml) conc. sulfuric acid (3 ml) was added The mixture was heated under reflux for 3 hrs The solvent was evaporated under reduced pressure, water was added under ice- cooling The solution was extracted with ethyl acetate The extract was washed with saturated brine dried by adding sodium sulfate The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→3/1)

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

Procedure: To a solution of 6-bromo-4-phenyl-3-isocoumarincarboxylic acid methyl ester (359 mg) in methanol (20 ml) was added 3-(4-aminomethylphenyl)propionic acid methyl ester (387 mg) and the mixture was stirred at room temperature for 18 hr. The solvent was evaporated under reduced pressure, 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried by adding sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was dissolved in methanol (30 ml) and conc. sulfuric acid (3 ml) was added. The mixture was heated under reflux for 3 hrs. The solvent was evaporated under reduced pressure, water was added under ice-cooling and the mixture was neutralized with potassium carbonate. The solution was extracted with ethyl acetate. The extract was washed with saturated brine and dried by adding sodium sulfate. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→3/1) to give the title compound (425 mg, 80%). The solvent was evaporated under reduced pressure, 1N hydrochloric acid was added the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried by adding sodium sulfate The solvent was evaporated under reduced pressure the obtained residue was dissolved in methanol (30 ml) conc. sulfuric acid (3 ml) was added The mixture was heated under reflux for 3 hrs The solvent was evaporated under reduced pressure, water was added under ice- cooling The solution was extracted with ethyl acetate The extract was washed with saturated brine dried by adding sodium sulfate The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→3/1)

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

Procedure: The title compound was prepared following the procedure A using 4-dec-1-ynylbenz-aldehyde and methyl 3-[4-(aminomethyl)phenyl]propanoate (purification by flash chromatography on SiO2, EtOAc/c-Hex 20/80) as a yellow oil (53%). 1H NMR (CDCl3) δ: 7.28 (d, J=8.3 Hz, 2H), 7.23-7.13 (m, 4H), 7.08 (d, J=7.9 Hz, 2H), 3.70 (s, 2H), 3.66 (s, 2H), 3.59 (s, 3H), 2.86 (t, J=8.3 Hz, 2H), 2.55 (t, J=7.2 Hz, 2H), 2.32 (t, J=7.2 Hz, 2H), 1.56-1.46 (m, 2H), 1.43-1.31 (m, 2H), 0.86-0.76 (m, 3H). M+ (ESI): 420.4. HPLC, Rt: 4.5 min (purity: 99.5%).

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

Procedure: To solution of methyl (2E)-3-(4-cyanophenyl)acrylate (18 g, 0.096 mol) in methanol (200 ml) was added Pd/C (1.8 g) and hydrogenated under a pressure of 50 psi of hydrogen for 12 h. The catalyst was filtered off and the filtrate was concentrated to a residue. The residue was purified by chromatography (SiO2, chloroform/methanol 9/1) to yield the title compound as a liquid (16 g, 86%). TLC:CHCl3/MeOH (9/1); Rf: 0.3 The catalyst was filtered off the filtrate was concentrated to a residue The residue was purified by chromatography (SiO2, chloroform/methanol 9/1)

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

Procedure: To solution of methyl (2E)-3-(4-cyanophenyl)acrylate (18 g, 0.096 mol) in methanol (200 ml) was added Pd/C (1.8 g) and hydrogenated under a pressure of 50 psi of hydrogen for 12 h. The catalyst was filtered off and the filtrate was concentrated to a residue. The residue was purified by chromatography (SiO2, chloroform/methanol 9/1) to yield the title compound as a liquid (16 g, 86%). TLC:CHCl3/MeOH (9/1); Rf: 0.3 The catalyst was filtered off the filtrate was concentrated to a residue The residue was purified by chromatography (SiO2, chloroform/methanol 9/1)

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

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

Procedure: To a solution of 6-bromo-4-phenyl-3-isocoumarincarboxylic acid methyl ester (359 mg) in methanol (20 ml) was added 3-(4-aminomethylphenyl)propionic acid methyl ester (387 mg) and the mixture was stirred at room temperature for 18 hr. The solvent was evaporated under reduced pressure, 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine and dried by adding sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was dissolved in methanol (30 ml) and conc. sulfuric acid (3 ml) was added. The mixture was heated under reflux for 3 hrs. The solvent was evaporated under reduced pressure, water was added under ice-cooling and the mixture was neutralized with potassium carbonate. The solution was extracted with ethyl acetate. The extract was washed with saturated brine and dried by adding sodium sulfate. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→3/1) to give the title compound (425 mg, 80%). The solvent was evaporated under reduced pressure, 1N hydrochloric acid was added the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried by adding sodium sulfate The solvent was evaporated under reduced pressure the obtained residue was dissolved in methanol (30 ml) conc. sulfuric acid (3 ml) was added The mixture was heated under reflux for 3 hrs The solvent was evaporated under reduced pressure, water was added under ice- cooling The solution was extracted with ethyl acetate The extract was washed with saturated brine dried by adding sodium sulfate The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=19/1→3/1)

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

Procedure: The title compound was prepared following the procedure A using 4-dec-1-ynylbenz-aldehyde and methyl 3-[4-(aminomethyl)phenyl]propanoate (purification by flash chromatography on SiO2, EtOAc/c-Hex 20/80) as a yellow oil (53%). 1H NMR (CDCl3) δ: 7.28 (d, J=8.3 Hz, 2H), 7.23-7.13 (m, 4H), 7.08 (d, J=7.9 Hz, 2H), 3.70 (s, 2H), 3.66 (s, 2H), 3.59 (s, 3H), 2.86 (t, J=8.3 Hz, 2H), 2.55 (t, J=7.2 Hz, 2H), 2.32 (t, J=7.2 Hz, 2H), 1.56-1.46 (m, 2H), 1.43-1.31 (m, 2H), 0.86-0.76 (m, 3H). M+ (ESI): 420.4. HPLC, Rt: 4.5 min (purity: 99.5%).

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

Procedure: To solution of methyl (2E)-3-(4-cyanophenyl)acrylate (18 g, 0.096 mol) in methanol (200 ml) was added Pd/C (1.8 g) and hydrogenated under a pressure of 50 psi of hydrogen for 12 h. The catalyst was filtered off and the filtrate was concentrated to a residue. The residue was purified by chromatography (SiO2, chloroform/methanol 9/1) to yield the title compound as a liquid (16 g, 86%). TLC:CHCl3/MeOH (9/1); Rf: 0.3 The catalyst was filtered off the filtrate was concentrated to a residue The residue was purified by chromatography (SiO2, chloroform/methanol 9/1)