2-ethyl-1H-pyrrole

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

Procedure: To a solution of 2-ethyl-1H-pyrrole in toluene (120 mL) was added dropwise 1M methylmagnesium bromide in tetrahydrofuran (170 mL) in a dry ice-acetone bath below −60° C. over 30 minutes. Then the mixture was stirred in an ice-water bath for 40 minutes. To this reaction mixture was added S-(2-pyridinyl) 4-cyanobenzenecarbothioate (15.2 g) portionwise over 10 minutes in a dryice-acetone bath. After 1.5 hours stirring, saturated ammonium chloride (100 mL) was added therein and the reaction mixture was allowed to ambient temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with 1N sodium hydroxide (100 mL) twice, water, and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was triturated with isopropyl ether to give 4-[(5-ethyl-1H-pyrrol-2-yl)carbonyl]benzonitrile (12.7 g) as a pale yellow solid. After 1.5 hours stirring was allowed to ambient temperature The mixture was partitioned between ethyl acetate and water The organic layer was washed with 1N sodium hydroxide (100 mL) twice water, and brine, dried over magnesium sulfate evaporated in vacuo The residue was triturated with isopropyl ether

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Chloroaniline (4.5 g, 35.4 mmole) was combined with tetrahydrofuran (80 ml) under nitrogen and cooled to -78° C. Chlorosulfonyl isocyanate (3.0 ml, 35.4 mmole) was added and the mixture stirred 1 hour at -78° C. 2-Ethylpyrrole (3.66 g, 38.9 mmole) was added and the mixture allowed to warm to room temperature and then stirred for 2 hours. The reaction was quenched with water and then concentrated. The residue was dissolved in methylene chloride (100 ml) which was extracted with three 100 ml portions of aqueous NaOH. The aqueous layer was acidifed and extracted with methylene chloride. The organic layers were combined and washed with two 100 ml portions of water. The organic layer was then dried over Na2SO4, filtered and concentrated. The resulting dark oil was flashed chromatographed over silica eluding with 4% methanol/methylene chloride. Removal of solvent provided 0.64 g of product. to warm to room temperature stirred for 2 hours The reaction was quenched with water concentrated The residue was dissolved in methylene chloride (100 ml) which was extracted with three 100 ml portions of aqueous NaOH extracted with methylene chloride washed with two 100 ml portions of water The organic layer was then dried over Na2SO4 filtered concentrated The resulting dark oil was flashed chromatographed over silica eluding with 4% methanol/methylene chloride Removal of solvent

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

Procedure: 2-Ethylpyrrole (4.75 g., 0.05 mole) was added dropwise to a stirred solution of glyoxylic acid hydrate (2.3 g., 0.025 mole) in 0.880 sp. gr. ammonia solution (25 ml.) at 50°. The mixture was stirred at 50° for 4 hours, then cooled, acidified to pH 5.5 with concentrated hydrochloric acid and filtered. The resulting solid was washed with water, triturated with cold, then hot; methanol and dried in vacuo to afford DL-2-(5-ethyl-2-pyrrolyl)glycine (1.8 g., 43%), M.P. 188° (decomp.). at 50° cooled filtered The resulting solid was washed with water triturated with cold, then hot methanol and dried in vacuo

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

Procedure: To a solution of 2-ethyl-1H-pyrrole in toluene (120 mL) was added dropwise 1M methylmagnesium bromide in tetrahydrofuran (170 mL) in a dry ice-acetone bath below −60° C. over 30 minutes. Then the mixture was stirred in an ice-water bath for 40 minutes. To this reaction mixture was added S-(2-pyridinyl) 4-cyanobenzenecarbothioate (15.2 g) portionwise over 10 minutes in a dryice-acetone bath. After 1.5 hours stirring, saturated ammonium chloride (100 mL) was added therein and the reaction mixture was allowed to ambient temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with 1N sodium hydroxide (100 mL) twice, water, and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was triturated with isopropyl ether to give 4-[(5-ethyl-1H-pyrrol-2-yl)carbonyl]benzonitrile (12.7 g) as a pale yellow solid. After 1.5 hours stirring was allowed to ambient temperature The mixture was partitioned between ethyl acetate and water The organic layer was washed with 1N sodium hydroxide (100 mL) twice water, and brine, dried over magnesium sulfate evaporated in vacuo The residue was triturated with isopropyl ether

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

Procedure: To a solution of 2-ethyl-1H-pyrrole in toluene (120 mL) was added dropwise 1M methylmagnesium bromide in tetrahydrofuran (170 mL) in a dry ice-acetone bath below −60° C. over 30 minutes. Then the mixture was stirred in an ice-water bath for 40 minutes. To this reaction mixture was added S-(2-pyridinyl) 4-cyanobenzenecarbothioate (15.2 g) portionwise over 10 minutes in a dryice-acetone bath. After 1.5 hours stirring, saturated ammonium chloride (100 mL) was added therein and the reaction mixture was allowed to ambient temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with 1N sodium hydroxide (100 mL) twice, water, and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was triturated with isopropyl ether to give 4-[(5-ethyl-1H-pyrrol-2-yl)carbonyl]benzonitrile (12.7 g) as a pale yellow solid. After 1.5 hours stirring was allowed to ambient temperature The mixture was partitioned between ethyl acetate and water The organic layer was washed with 1N sodium hydroxide (100 mL) twice water, and brine, dried over magnesium sulfate evaporated in vacuo The residue was triturated with isopropyl ether

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

Procedure: To a solution of 2-ethyl-1H-pyrrole in toluene (120 mL) was added dropwise 1M methylmagnesium bromide in tetrahydrofuran (170 mL) in a dry ice-acetone bath below −60° C. over 30 minutes. Then the mixture was stirred in an ice-water bath for 40 minutes. To this reaction mixture was added S-(2-pyridinyl) 4-cyanobenzenecarbothioate (15.2 g) portionwise over 10 minutes in a dryice-acetone bath. After 1.5 hours stirring, saturated ammonium chloride (100 mL) was added therein and the reaction mixture was allowed to ambient temperature. The mixture was partitioned between ethyl acetate and water. The organic layer was washed with 1N sodium hydroxide (100 mL) twice, water, and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was triturated with isopropyl ether to give 4-[(5-ethyl-1H-pyrrol-2-yl)carbonyl]benzonitrile (12.7 g) as a pale yellow solid. After 1.5 hours stirring was allowed to ambient temperature The mixture was partitioned between ethyl acetate and water The organic layer was washed with 1N sodium hydroxide (100 mL) twice water, and brine, dried over magnesium sulfate evaporated in vacuo The residue was triturated with isopropyl ether