ethyl 4-bromo-1H-pyrrole-2-carboxylate

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

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1H-Pyrrole-2-carboxylic acid ethyl ester (10 g) was dissolved in carbon tetrachloride (50 ml). A carbon tetrachloride solution (50 ml) of bromine was added dropwise thereto on ice over 30 minutes. The reaction mixture was stirred at 25° C. for one hour. The suspension of reaction mixture was added dropwise to an ethanol solution (100 ml) of 10% sodium ethoxide on ice over 20 minutes. The solvent was concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate (40 ml) and water (20 ml). The organic layer was washed with an aqueous solution saturated with sodium chloride (10 ml), and then concentrated. The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (hexane/ethyl acetate). Thus, a brown solid was obtained (10 g, 99%). The suspension of reaction mixture The solvent was concentrated under reduced pressure The resulting residue was diluted with ethyl acetate (40 ml) and water (20 ml) The organic layer was washed with an aqueous solution saturated with sodium chloride (10 ml) concentrated The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (hexane/ethyl acetate) Thus, a brown solid was obtained (10 g, 99%)

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

Procedure: To a cooled (0° C.) solution of ethyl 4-bromo-1H-pyrrole-2-carboxylate (Belanger, P. Tetrahedron Lett. 1979, 20, 2505) (9.50 g, 43.6 mmol) in acetonitrile (200 mL) was added chlorosulfonyl isocyanate (3.87 mL, 43.6 mmol), drop wise. The reaction was allowed to warm to rt and stir for 17 h. The reaction was quenched with the addition of DMF (17 mL) and the reaction was heated (50° C.) for 2 h then cooled to rt and stirred an additional 2 h. The mixture was poured over ice water (500 mL) and was extracted with ethyl acetate (3×250 mL). The combined organics were washed with brine, dried (Na2SO4) and concentrated. The crude material was purified via flash chromatography on silica gel eluting with 10% to 25% ethyl acetate in hexanes to afford 7.88 g (74%) of the desired product. 1H NMR (300 MHz, DMSO-d6) δ 13.77 (br s, 1 H), 7.01 (s, 1 H), 4.28 (q, 2 H), 1.29 (t, 3 H). The reaction was quenched with the addition of DMF (17 mL) the reaction was heated (50° C.) for 2 h then cooled to rt stirred an additional 2 h The mixture was poured over ice water (500 mL) was extracted with ethyl acetate (3×250 mL) The combined organics were washed with brine dried (Na2SO4) concentrated The crude material was purified via flash chromatography on silica gel eluting with 10% to 25% ethyl acetate in hexanes

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

Procedure: Wash 60% mineral oil suspended sodium hydride (1.2 equiv; 1.1 g, 27.52 mmoles) with a small amount of iso-hexane (×2). Suspend in N,N-dimethylacetamide (15 mL) and chill in an ice-bath. Add ethyl 4-bromo-1H-pyrrole-2-carboxylate (5.0 g, 22.93 mmoles) portionwise over 15 minutes allowing gas evolution to subside between additions. Stir at room temperature for 15 minutes to give a brown solution. Add 2-(bromomethyl)-4-chloro-1-nitro-benzene (1.15 equiv; 6.61 g, 26.37 mmoles) in portions over 15 minutes and stir the resulting purple solution at room temperature for 2.5 h. Cool in an ice-bath and quench with water (10 mL). Partition between 1M hydrochloric acid (100 mL) and EtOAc (300 mL). Wash the organic layer with water (2×100 mL) then brine. Dry over Na2SO4 and decolorize with activated charcoal. Filter through celite and evaporate to give ethyl 4-bromo-1-(5-chloro-2-nitrobenzyl)-1H-pyrrole-2-carboxylate as a an orange oil (9.1 g, quantitative). 1H-NMR (CDCl3) δ: 8.12 (1H, d), 7.40 (1H, dd), 7.07 (1H, d), 6.92 (1H, d), 6.53 (1H, d), 5.87 (2H, s), 4.17 (2H, q), 1.25 (3H, t). Wash 60% mineral oil chill in an ice-bath to give a brown solution stir the resulting purple solution at room temperature for 2.5 h Cool in an ice-bath quench with water (10 mL) Partition between 1M hydrochloric acid (100 mL) and EtOAc (300 mL) Wash the organic layer with water (2×100 mL) Dry over Na2SO4 Filter through celite evaporate

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1H-Pyrrole-2-carboxylic acid ethyl ester (10 g) was dissolved in carbon tetrachloride (50 ml). A carbon tetrachloride solution (50 ml) of bromine was added dropwise thereto on ice over 30 minutes. The reaction mixture was stirred at 25° C. for one hour. The suspension of reaction mixture was added dropwise to an ethanol solution (100 ml) of 10% sodium ethoxide on ice over 20 minutes. The solvent was concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate (40 ml) and water (20 ml). The organic layer was washed with an aqueous solution saturated with sodium chloride (10 ml), and then concentrated. The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (hexane/ethyl acetate). Thus, a brown solid was obtained (10 g, 99%). The suspension of reaction mixture The solvent was concentrated under reduced pressure The resulting residue was diluted with ethyl acetate (40 ml) and water (20 ml) The organic layer was washed with an aqueous solution saturated with sodium chloride (10 ml) concentrated The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (hexane/ethyl acetate) Thus, a brown solid was obtained (10 g, 99%)

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

Procedure: To a solution of ethyl 1H-pyrrole-2-carboxylate (1.17 g) in carbon tetrachloride (40 ml), a solution of bromine (1.48 g) in carbon tetrachloride (80 ml) was added dropwise at −15° C., and the mixture was stirred for one hour. The mixture was warmed to a room temperature, and a 2-N sodium hydroxide aqueous solution (80 ml) was added thereto. The resulting mixture was subjected to extraction with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under a reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:6) to give ethyl 4-bromo-1H-pyrrole-2-carboxylate (700 mg, 38%). The resulting mixture was subjected to extraction with ethyl acetate the organic layer was dried over anhydrous magnesium sulfate concentrated under a reduced pressure The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:6)

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

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1H-Pyrrole-2-carboxylic acid ethyl ester (10 g) was dissolved in carbon tetrachloride (50 ml). A carbon tetrachloride solution (50 ml) of bromine was added dropwise thereto on ice over 30 minutes. The reaction mixture was stirred at 25° C. for one hour. The suspension of reaction mixture was added dropwise to an ethanol solution (100 ml) of 10% sodium ethoxide on ice over 20 minutes. The solvent was concentrated under reduced pressure. The resulting residue was diluted with ethyl acetate (40 ml) and water (20 ml). The organic layer was washed with an aqueous solution saturated with sodium chloride (10 ml), and then concentrated. The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (hexane/ethyl acetate). Thus, a brown solid was obtained (10 g, 99%). The suspension of reaction mixture The solvent was concentrated under reduced pressure The resulting residue was diluted with ethyl acetate (40 ml) and water (20 ml) The organic layer was washed with an aqueous solution saturated with sodium chloride (10 ml) concentrated The residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (hexane/ethyl acetate) Thus, a brown solid was obtained (10 g, 99%)