ethyl 5-bromo-1H-pyrrole-2-carboxylate

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available ethyl 1H-pyrrole-2-carboxylate (5.10 g, 30.7 mmol) was dissolved in a mixed solvent of tetrahydrofuran (120 mL) and methanol (60 mL), and cooled to 0° C. N-Bromosuccinimide (6.52 g, 30.7 mmol) was added, and stirring was carried out at room temperature for 18 hours under nitrogen atmosphere. Water (150 mL) and ethyl acetate (200 mL) were added, and the solution was separated. The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-30%) to afford the desired compound (3.20 g, yield 40%) as a white solid. the solution was separated The organic layer was washed with saturated brine subsequently dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-30%)

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available ethyl 1H-pyrrole-2-carboxylate (5.10 g, 30.7 mmol) was dissolved in a mixed solvent of tetrahydrofuran (120 mL) and methanol (60 mL), and cooled to 0° C. N-Bromosuccinimide (6.52 g, 30.7 mmol) was added, and stirring was carried out at room temperature for 18 hours under nitrogen atmosphere. Water (150 mL) and ethyl acetate (200 mL) were added, and the solution was separated. The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-30%) to afford the desired compound (3.20 g, yield 40%) as a white solid. the solution was separated The organic layer was washed with saturated brine subsequently dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-30%)

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

Procedure: A mixture of ethyl 5-bromo-1H-pyrrole-2-carboxylate (0.13 g, 0.64 mmol), 2-bromo-1-(4-methoxyphenyl)ethanone (160 mg, 0.69 mmol) and potassium carbonate (132 mg, 0.95 mmol) in N,N-dimethylformamide (4 mL) was stirred at room temperature overnight. At this time, the light brown reaction mixture was quenched with water. The resulting precipitate was collected by filtration and dried in vacuo. The resulting solid was dissolved in methylene chloride, concentrated in vacuo and then triturated with diethyl ether. The resulting solid was collected by filtration and dried in vacuo to afford 5-bromo-1-[2-(4-methoxy-phenyl)-2-oxo-ethyl]-1H-pyrrole-2-carboxylic acid methyl ester (155 mg, 69%) as light brown solid. 1H NMR (chloroform-d) δ ppm 8.00 (d, J=8.8 Hz, 2H), 6.96-7.07 (m, 3H), 6.85 (d, J=1.8 Hz, 1H), 5.71 (s, 2H), 3.91 (s, 3H), 3.75 (s, 3H). At this time, the light brown reaction mixture was quenched with water The resulting precipitate was collected by filtration dried in vacuo The resulting solid was dissolved in methylene chloride concentrated in vacuo triturated with diethyl ether The resulting solid was collected by filtration dried in vacuo

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

Procedure: Na2CO3 (97.5 mg, 0.92 mmol) was added to a stirred solution of 5-bromo-1H-pyrrole-2-carboxylic acid ethyl ester (100 mg, 0.46 mmol) in toluene: H2O (5:1, 11 mL). Pd (PPh3)4 (53 mg, 0.046 mmol) and phenylboronic acid (84.3 mg, 0.7 mmol) were then added and the reaction mixture was heated to reflux for 2 hrs. The reaction mixture was then diluted with water and the product was extracted with ethyl acetate. The organic layer was washed with saturated brine solution, dried over sodium sulphate and concentrated to get the residue. The residue obtained was purified by column chromatography (using silica gel of 60-120 mesh and 5% EtOAc in Hexane as eluent) afford 67 mg (67.95% yield) of 5-phenyl-1H-pyrrole-2-carboxylic acid ethyl ester. 1H NMR (CDCl3): δ 9.4 (s, 1H), 7.64 (d, 2H), 7.48 (t, 2H), 7.36 (d, 11H), 7.0 (s, 1H), 6.58 (s, 1H), 4.4 (q, 2H), 1.4 (t, 3H). the reaction mixture was heated to reflux for 2 hrs the product was extracted with ethyl acetate The organic layer was washed with saturated brine solution dried over sodium sulphate concentrated to get the residue The residue obtained was purified by column chromatography (using silica gel of 60-120 mesh and 5% EtOAc in Hexane as eluent)

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

Procedure: NBS (0.15 mg, 0.83 mmol) was added to a stirred cold (0-5° C.) solution of 1H-pyrrole-2-carboxylic acid ethyl ester (200 mg, 1.44 mmol) in THF: MeOH (2:1, 24 mL). Stirring was continued at same temperature for 2 hrs. Solvent was removed under vacuum to get the residue. The residue obtained was purified by column chromatography (using silica gel of 200-430 mesh and 10% Ether in Hexane as eluent) to afford 100 mg (31.95% yield) of 5-bromo-1H-pyrrole-2-carboxylic acid ethyl ester. 1H NMR (CDCl3): δ 9.4 (bs, 1H), 6.8 (s, 1H), 6.2 (s, 1H), 4.4-4.2 (q, 2H), 1.4 (t, 3H). Solvent was removed under vacuum to get the residue The residue obtained was purified by column chromatography (using silica gel of 200-430 mesh and 10% Ether in Hexane as eluent)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Commercially available ethyl 1H-pyrrole-2-carboxylate (5.10 g, 30.7 mmol) was dissolved in a mixed solvent of tetrahydrofuran (120 mL) and methanol (60 mL), and cooled to 0° C. N-Bromosuccinimide (6.52 g, 30.7 mmol) was added, and stirring was carried out at room temperature for 18 hours under nitrogen atmosphere. Water (150 mL) and ethyl acetate (200 mL) were added, and the solution was separated. The organic layer was washed with saturated brine, and subsequently dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-30%) to afford the desired compound (3.20 g, yield 40%) as a white solid. the solution was separated The organic layer was washed with saturated brine subsequently dried over anhydrous magnesium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified silica gel column chromatography (elution solvent: ethyl acetate/hexane=5%-30%)