methyl 4-iodo-1H-pyrrole-2-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:0.00; 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: 4-Iodo-1H-pyrrole-2-carboxylic acid methyl ester 57d (25.1 g, 100 mmol) was dissolved in 150 mL of dichloromethane followed by addition of triethylamine (30.6 mL, 220 mmol), 4-dimethylaminopyridine (1.22 g, 10 mmol) and p-toluenesulfonic acid (21 g, 110 mmol). The reaction mixture was reacted at 20° C. overnight. The reaction was monitored by TLC until the disappearance of the starting materials and quenched by addition of 30 mL of hydrochloric acid (1 N). The mixture was extracted with dichloromethane (50 mL×3). The combined organic extracts were washed with saturated aqueous sodium carbonate and saturated brine successively, dried over anhydrous sodium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 4-iodo-1-(toluene-4-sulfonyl)-1H-pyrrole-2-carboxylic acid methyl ester 57e (32.5 g, yield 80.2%) as a white solid. The reaction mixture was reacted at 20° C. overnight quenched by addition of 30 mL of hydrochloric acid (1 N) The mixture was extracted with dichloromethane (50 mL×3) The combined organic extracts were washed with saturated aqueous sodium carbonate and saturated brine successively dried over anhydrous sodium sulfate filtered to remove the drying agent concentrated under reduced pressure The residue was purified by silica gel column chromatography

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

Procedure: 2,2,2-Trichloro-1-(4-iodo-1H-pyrrol-2-yl)-ethanone 57c (47 g, 136 mmol) was dissolved in 265 mL of methanol followed by dropwise addition of a solution of sodium methoxide (17.23 g, 163 mmol) in 200 mL of methanol. The reaction mixture was stirred at room temperature for 1 hour. The reaction was monitored by TLC until the disappearance of the starting materials. The mixture was concentrated under reduced pressure. The residue was diluted with 20 mL of water and then extracted with ethyl acetate (30 mL×3). The combined organic extracts were washed with saturated brine, dried over anhydrous sodium sulfate, filtered to remove the drying agent and concentrated under reduced pressure to obtain the title compound 4-iodo-1H-pyrrole-2-carboxylic acid methyl ester 57d (32.2 g, yield 92.5%) as a grey solid. The mixture was concentrated under reduced pressure The residue was diluted with 20 mL of water extracted with ethyl acetate (30 mL×3) The combined organic extracts were washed with saturated brine dried over anhydrous sodium sulfate filtered to remove the drying agent concentrated under reduced pressure

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

Procedure: 4-Iodo-1H-pyrrole-2-carboxylic acid methyl ester (24.6 g, 98 mmol, 1.0 equivalent) was dissolved in dichloromethane (150 mL) and triethylamine (30 mL, 215.6 mmol, 2.2 equivalents). 4-(Dimethylamino)pyridine (1.2 g, 9.8 mmol, 0.1 equivalent) and p-toluenesulfonylchloride (20.6 g, 107.8 mmol, 1.1 equivalents) were added and the reaction mixture was stirred for 16 hours at room temperature. The reaction was quenched with 1 M HCl and the organic layer was washed with aqueous sodium bicarbonate and brine. After drying over magnesium sulfate, the solvent was removed under reduced pressure and the residue was crystallized from tert-butylmethyl ether, yielding the title compound as a pale yellow solid (30 g, 75%). Rt(min) 8.259 minutes. The reaction was quenched with 1 M HCl the organic layer was washed with aqueous sodium bicarbonate and brine After drying over magnesium sulfate the solvent was removed under reduced pressure the residue was crystallized from tert-butylmethyl ether

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

Procedure: 4-Iodo-1H-pyrrole-2-carboxylic acid methyl ester (24.6 g, 98 mmol, 1.0 equivalent) was dissolved in dichloromethane (150 mL) and triethylamine (30 mL, 215.6 mmol, 2.2 equivalents). 4-(Dimethylamino)pyridine (1.2 g, 9.8 mmol, 0.1 equivalent) and p-toluenesulfonylchloride (20.6 g, 107.8 mmol, 1.1 equivalents) were added and the reaction mixture was stirred for 16 hours at room temperature. The reaction was quenched with 1 M HCl and the organic layer was washed with aqueous sodium bicarbonate and brine. After drying over magnesium sulfate, the solvent was removed under reduced pressure and the residue was crystallized from tert-butylmethyl ether, yielding the title compound as a pale yellow solid (30 g, 75%). Rt(min) 8.259 minutes. The reaction was quenched with 1 M HCl the organic layer was washed with aqueous sodium bicarbonate and brine After drying over magnesium sulfate the solvent was removed under reduced pressure the residue was crystallized from tert-butylmethyl ether

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

Procedure: To a stirred solution of 2,2,2-trichloro-1-(4-iodo-1H-pyrrol-2-yl)ethanone (68 g, 201 mmol, 1.0 equivalent) in dry methanol (400 mL) under nitrogen, was added a solution of sodium methoxide in methanol (4.37 M, 54 mL, 235 mmol, 1.2 equivalents) over 10 minutes. The resulting mixture was stirred at room temperature for 1 hour. The volatiles were removed under reduced pressure and the crude was then partitioned between water and tert-butylmethyl ether. The organic phase was separated, washed two times with water, saturated sodium chloride, dried over sodium sulfate, filtered and concentrated under vacuum to afford the title compound (48 g, 96%) as a colorless solid, that was used directly without further purification. The volatiles were removed under reduced pressure the crude was then partitioned between water and tert-butylmethyl ether The organic phase was separated washed two times with water, saturated sodium chloride dried over sodium sulfate filtered concentrated under vacuum

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

Procedure: 780 mg (25.9 mmol) of sodium hydride (80% in oil) and 20 ml of DMF were introduced into a three-necked flask, a solution of 6.5 g (25.9 mmol) of methyl 4-iodo-2-pyrrolecarboxylate in 50 ml of DMF was added dropwise and stirring was carried out until gas evolution has ceased. 2.1 ml (33.6 mmol) of iodomethane were then added and stirring was carried out at room temperature for two hours. The reaction mixture was poured into water and extracted with ethyl ether. The organic phase was separated by settling, dried over magnesium sulfate and was evaporated. The residue obtained was purified by chromatography on a silica column eluted with a mixture of dichloromethane and hexane (40/60). 4.5 g (65%) of methyl N-methyl-4-iodo-2-pyrrolecarboxylate, with a melting point of 64°-65° C., were recovered. stirring extracted with ethyl ether The organic phase was separated dried over magnesium sulfate was evaporated The residue obtained was purified by chromatography on a silica column eluted with a mixture of dichloromethane and hexane (40/60) 4.5 g (65%) of methyl N-methyl-4-iodo-2-pyrrolecarboxylate, with a melting point of 64°-65° C., were recovered

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

Procedure: 8.2 g (24 mmol) of 4-iodo-2-trichloroacetylpyrrole and 100 ml of methanol were introduced into a round-bottomed flask and 2 g (36 mmol) of sodium methoxide were added. Stirring was carried out at room temperature for four hours, the reaction mixture was evaporated to dryness and the residue obtained was taken up in water and ethyl ether. The organic phase was separated by settling, dried over magnesium sulfate and evaporated. The residue obtained was triturated in heptane and filtered. 4.9 g (81%) of the expected ester, with a melting point of 77°-78° C., were recovered. the reaction mixture was evaporated to dryness the residue obtained The organic phase was separated dried over magnesium sulfate evaporated The residue obtained was triturated in heptane filtered 4.9 g (81%) of the expected ester, with a melting point of 77°-78° C., were recovered