methyl 5-bromo-1H-pyrrole-3-carboxylate

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

Procedure: POCl3 (Aldrich; 0.531 mL, 5.70 mmol) was added (dropwise, over 1 min) to DMF (1.32 mL, 17.10 mmol) under argon at 0° C., and the resulting solution was stirred at 0° C. for 15 min. This solution was then added (dropwise, over 1 min) to a dark-brown solution of methyl 5-bromo-1H-pyrrole-3-carboxylate (581 mg, 2.85 mmol) in ACN (6.0 mL) at 23° C., and the resulting solution was stirred under argon at 50° C. for 3 h. The reaction mixture was then poured into 10:1 water/sat. aq. NaHCO3 (50 mL) and extracted with DCM (3×50 mL). The combined extracts were dried over Na2SO4, filtered, and concentrated onto silica gel. Chromatographic purification (silica gel, 0-30% EtOAc/hexanes) furnished methyl 5-bromo-2-formyl-1H-pyrrole-3-carboxylate (245 mg, 1.05 mmol, 37% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 10.09 (1H, s), 9.56 (1H, br. s.), 6.72 (1H, d, J=2.7 Hz), 3.90 (3H, s). m/z (ESI, +ve) 231.9/234.1 (M+H)+. the resulting solution was stirred under argon at 50° C. for 3 h aq. NaHCO3 (50 mL) and extracted with DCM (3×50 mL) The combined extracts were dried over Na2SO4 filtered concentrated onto silica gel Chromatographic purification (silica gel, 0-30% EtOAc/hexanes)

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: NBS (Aldrich; 1.201 g, 6.75 mmol) was added in one portion to a solution of methyl 1H-pyrrole-3-carboxylate (Aldrich; 0.844 g, 6.75 mmol) in THF (10 mL), and the resulting solution was stirred at 23° C. for 1.5 h. THF was removed in vacuo, and the residue was taken up in DCM (50 mL) and washed with 10:1 water/sat. aq. NaHCO3 (50 mL). The organic layer was separated, and the aq. layer was extracted with DCM (2×40 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated onto silica gel. Chromatographic purification (silica gel, 0-50% EtOAc/hexanes) furnished methyl 5-bromo-1H-pyrrole-3-carboxylate (924.2 mg, 4.53 mmol, 67% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.41 (1H, br. s.), 7.36 (1H, dd, J=2.9, 1.8 Hz), 6.60 (1H, dd, J=2.5, 1.8 Hz), 3.81 (3H, s). m/z (ESI, +ve) 203.9/205.9 (M+H)+. THF was removed in vacuo washed with 10:1 water/ The organic layer was separated the aq. layer was extracted with DCM (2×40 mL) The combined organic extracts were dried over Na2SO4 filtered concentrated onto silica gel Chromatographic purification (silica gel, 0-50% EtOAc/hexanes)

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: NBS (Aldrich; 1.201 g, 6.75 mmol) was added in one portion to a solution of methyl 1H-pyrrole-3-carboxylate (Aldrich; 0.844 g, 6.75 mmol) in THF (10 mL), and the resulting solution was stirred at 23° C. for 1.5 h. THF was removed in vacuo, and the residue was taken up in DCM (50 mL) and washed with 10:1 water/sat. aq. NaHCO3 (50 mL). The organic layer was separated, and the aq. layer was extracted with DCM (2×40 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated onto silica gel. Chromatographic purification (silica gel, 0-50% EtOAc/hexanes) furnished methyl 5-bromo-1H-pyrrole-3-carboxylate (924.2 mg, 4.53 mmol, 67% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 8.41 (1H, br. s.), 7.36 (1H, dd, J=2.9, 1.8 Hz), 6.60 (1H, dd, J=2.5, 1.8 Hz), 3.81 (3H, s). m/z (ESI, +ve) 203.9/205.9 (M+H)+. THF was removed in vacuo washed with 10:1 water/ The organic layer was separated the aq. layer was extracted with DCM (2×40 mL) The combined organic extracts were dried over Na2SO4 filtered concentrated onto silica gel Chromatographic purification (silica gel, 0-50% EtOAc/hexanes)

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

Procedure: A solution (30 mL) of methyl 1H-pyrrole-3-carboxylate (3.06 g) in tetrahydrofuran was cooled to −78° C., N-bromosuccinimide (4.38 g) and then pyridine (3 drops) were added, and the mixture was stirred at the same temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=5:1) to give the title compound as a pale-yellow solid (yield 3.08 g, 62%). the mixture was extracted with ethyl acetate The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=5:1)

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

Procedure: A solution (30 mL) of methyl 1H-pyrrole-3-carboxylate (3.06 g) in tetrahydrofuran was cooled to −78° C., N-bromosuccinimide (4.38 g) and then pyridine (3 drops) were added, and the mixture was stirred at the same temperature for 1 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=5:1) to give the title compound as a pale-yellow solid (yield 3.08 g, 62%). the mixture was extracted with ethyl acetate The extract was washed with saturated aqueous sodium hydrogencarbonate solution, water and saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent:hexane-ethyl acetate=5:1)

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

Procedure: Using methyl 5-bromo-1H-pyrrole-3-carboxylate (2.89 g), sodium hydride (60% in oil, 850 mg), 15-crown-5 (4.69 g) and 3-methylsulfonylbenzenesulfonyl chloride (4.38 g), a procedure as in Reference Example 146 was performed to give the title compound as white crystals (yield 5.50 g, 92%).

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

Procedure: Using methyl 5-bromo-1H-pyrrole-3-carboxylate (2.89 g), sodium hydride (60% in oil, 850 mg), 15-crown-5 (4.69 g) and 3-methylsulfonylbenzenesulfonyl chloride (4.38 g), a procedure as in Reference Example 146 was performed to give the title compound as white crystals (yield 5.50 g, 92%).

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

Procedure: A solution (70 mL) of methyl 1H-pyrrole-3-carboxylate (4.48 g) in tetrahydrofuran was cooled to −78° C., N-bromosuccinimide (6.30 g) was added, pyridine (5 drops) was added, and the mixture was left standing in a freezer (−20° C.) for 3 days. The reaction mixture was concentrated under reduced pressure, water was added to the residue and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=9:1→1:1) to give the title compound as a pale-yellow solid (yield 3.59 g, 49%). the mixture was left The reaction mixture was concentrated under reduced pressure, water was added to the residue the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous sodium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=9:1→1:1)

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