methyl 3-pyrrolidin-1-ylprop-2-enoate

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

Procedure: First a solution of 15.5 g of methyl 3-(1-pyrrolidinyl)acrylate in 25 ml of dioxane is added dropwise, and then 10.5 g of triethylamine are added to a solution of 22.75 g of 2,4-dichloro-5-fluorobenzoyl chloride in 80 ml of anhydrous dioxane, while cooling in ice and stirring. The mixture is stirred at room temperature for 1 hour, heated to boiling under reflux for 30 minutes, and the solvent is removed by distillation in vacuo, and the residue is taken up in methylene chloride/H2O. The phases are separated and the aqueous solution is again extracted with methylene chloride. The combined organic phases are washed with water, dried with sodium sulphate, and the methylene chloride is removed in vacuo. The crystalline residue is recrystallized from cyclohexane. 19.6 g of methyl 3-(1-pyrrolidinyl)-2-(2,4-dichloro-5-fluorobenzoyl)acrylate of melting point 74°-76° C. are obtained. while cooling in ice The mixture is stirred at room temperature for 1 hour heated under reflux for 30 minutes the solvent is removed by distillation in vacuo The phases are separated the aqueous solution is again extracted with methylene chloride The combined organic phases are washed with water dried with sodium sulphate the methylene chloride is removed in vacuo The crystalline residue is recrystallized from cyclohexane

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

Procedure: First a solution of 15.5 g of methyl 3-(1-pyrrolidinyl)acrylate in 25 ml of dioxane is added dropwise, and then 10.5 g of triethylamine are added to a solution of 22.75 g of 2,4-dichloro-5-fluorobenzoyl chloride in 80 ml of anhydrous dioxane, while cooling in ice and stirring. The mixture is stirred at room temperature for 1 hour, heated to boiling under reflux for 30 minutes, and the solvent is removed by distillation in vacuo, and the residue is taken up in methylene chloride/H2O. The phases are separated and the aqueous solution is again extracted with methylene chloride. The combined organic phases are washed with water, dried with sodium sulphate, and the methylene chloride is removed in vacuo. The crystalline residue is recrystallized from cyclohexane. 19.6 g of methyl 3-(1-pyrrolidinyl)-2-(2,4-dichloro-5-fluorobenzoyl)acrylate of melting point 74°-76° C. are obtained. while cooling in ice The mixture is stirred at room temperature for 1 hour heated under reflux for 30 minutes the solvent is removed by distillation in vacuo The phases are separated the aqueous solution is again extracted with methylene chloride The combined organic phases are washed with water dried with sodium sulphate the methylene chloride is removed in vacuo The crystalline residue is recrystallized from cyclohexane

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

Procedure: To a solution of 1.05 g of 4-fluorobenzaldoxime (Beil. 7, I 132d, II 177d, III 863c) in 15 mL of chloroform were added 1.35 g of N-bromosuccinimide (NBS) and 0.04 mL of pyridine; the resulting mixture was stirred at r.t for 4 h under nitrogen atmosphere. After cooling at 0° C., 1.75 g of methyl β-pyrrolidinoacrylate (prepared as described in U.S. Pat. No. 4,144,047) and 1.26 mL of triethylamine were added and the suspension was stirred at r.t. for 18 h. The reaction mixture was diluted with 20 mL of 2 N hydrochloric acid, 20 mL of water; the organic layer was separated, washed again with 2 N hydrochloric acid and water, dried (sodium sulphate), and evaporated to dryness in vacuo. The crude was purified by flash chromatography (toluene-dichloromethane 1:9) to afford the title compound (47%) as an oil. the suspension was stirred at r.t. for 18 h the organic layer was separated washed again with 2 N hydrochloric acid and water dried (sodium sulphate) evaporated to dryness in vacuo The crude was purified by flash chromatography (toluene-dichloromethane 1:9)

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

Procedure: To a solution of 1.05 g of 4-fluorobenzaldoxime (Beil. 7, I 132d, II 177d, III 863c) in 15 mL of chloroform were added 1.35 g of N-bromosuccinimide (NBS) and 0.04 mL of pyridine; the resulting mixture was stirred at r.t for 4 h under nitrogen atmosphere. After cooling at 0° C., 1.75 g of methyl β-pyrrolidinoacrylate (prepared as described in U.S. Pat. No. 4,144,047) and 1.26 mL of triethylamine were added and the suspension was stirred at r.t. for 18 h. The reaction mixture was diluted with 20 mL of 2 N hydrochloric acid, 20 mL of water; the organic layer was separated, washed again with 2 N hydrochloric acid and water, dried (sodium sulphate), and evaporated to dryness in vacuo. The crude was purified by flash chromatography (toluene-dichloromethane 1:9) to afford the title compound (47%) as an oil. the suspension was stirred at r.t. for 18 h the organic layer was separated washed again with 2 N hydrochloric acid and water dried (sodium sulphate) evaporated to dryness in vacuo The crude was purified by flash chromatography (toluene-dichloromethane 1:9)

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

Procedure: First a solution of 15.5 g of methyl 3-(1-pyrrolidinyl)acrylate in 25 ml of dioxane is added dropwise, and then 10.5 g of triethylamine are added to a solution of 22.75 g of 2,4-dichloro-5-fluorobenzoyl chloride in 80 ml of anhydrous dioxane, while cooling in ice and stirring. The mixture is stirred at room temperature for 1 hour, heated to boiling under reflux for 30 minutes, and the solvent is removed by distillation in vacuo, and the residue is taken up in methylene chloride/H2O. The phases are separated and the aqueous solution is again extracted with methylene chloride. The combined organic phases are washed with water, dried with sodium sulphate, and the methylene chloride is removed in vacuo. The crystalline residue is recrystallized from cyclohexane. 19.6 g of methyl 3-(1-pyrrolidinyl)-2-(2,4-dichloro-5-fluorobenzoyl)acrylate of melting point 74°-76° C. are obtained. while cooling in ice The mixture is stirred at room temperature for 1 hour heated under reflux for 30 minutes the solvent is removed by distillation in vacuo The phases are separated the aqueous solution is again extracted with methylene chloride The combined organic phases are washed with water dried with sodium sulphate the methylene chloride is removed in vacuo The crystalline residue is recrystallized from cyclohexane

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

Procedure: To a solution of 1.05 g of 4-fluorobenzaldoxime (Beil. 7, I 132d, II 177d, III 863c) in 15 mL of chloroform were added 1.35 g of N-bromosuccinimide (NBS) and 0.04 mL of pyridine; the resulting mixture was stirred at r.t for 4 h under nitrogen atmosphere. After cooling at 0° C., 1.75 g of methyl β-pyrrolidinoacrylate (prepared as described in U.S. Pat. No. 4,144,047) and 1.26 mL of triethylamine were added and the suspension was stirred at r.t. for 18 h. The reaction mixture was diluted with 20 mL of 2 N hydrochloric acid, 20 mL of water; the organic layer was separated, washed again with 2 N hydrochloric acid and water, dried (sodium sulphate), and evaporated to dryness in vacuo. The crude was purified by flash chromatography (toluene-dichloromethane 1:9) to afford the title compound (47%) as an oil. the suspension was stirred at r.t. for 18 h the organic layer was separated washed again with 2 N hydrochloric acid and water dried (sodium sulphate) evaporated to dryness in vacuo The crude was purified by flash chromatography (toluene-dichloromethane 1:9)

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

Procedure: To a solution of 1.05 g of 4-fluorobenzaldoxime (Beil. 7, I 132d, II 177d, III 863c) in 15 mL of chloroform were added 1.35 g of N-bromosuccinimide (NBS) and 0.04 mL of pyridine; the resulting mixture was stirred at r.t for 4 h under nitrogen atmosphere. After cooling at 0° C., 1.75 g of methyl β-pyrrolidinoacrylate (prepared as described in U.S. Pat. No. 4,144,047) and 1.26 mL of triethylamine were added and the suspension was stirred at r.t. for 18 h. The reaction mixture was diluted with 20 mL of 2 N hydrochloric acid, 20 mL of water; the organic layer was separated, washed again with 2 N hydrochloric acid and water, dried (sodium sulphate), and evaporated to dryness in vacuo. The crude was purified by flash chromatography (toluene-dichloromethane 1:9) to afford the title compound (47%) as an oil. the suspension was stirred at r.t. for 18 h the organic layer was separated washed again with 2 N hydrochloric acid and water dried (sodium sulphate) evaporated to dryness in vacuo The crude was purified by flash chromatography (toluene-dichloromethane 1:9)

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

Procedure: First a solution of 15.5 g of methyl 3-(1-pyrrolidinyl)acrylate in 25 ml of dioxane is added dropwise, and then 10.5 g of triethylamine are added to a solution of 22.75 g of 2,4-dichloro-5-fluorobenzoyl chloride in 80 ml of anhydrous dioxane, while cooling in ice and stirring. The mixture is stirred at room temperature for 1 hour, heated to boiling under reflux for 30 minutes, and the solvent is removed by distillation in vacuo, and the residue is taken up in methylene chloride/H2O. The phases are separated and the aqueous solution is again extracted with methylene chloride. The combined organic phases are washed with water, dried with sodium sulphate, and the methylene chloride is removed in vacuo. The crystalline residue is recrystallized from cyclohexane. 19.6 g of methyl 3-(1-pyrrolidinyl)-2-(2,4-dichloro-5-fluorobenzoyl)acrylate of melting point 74°-76° C. are obtained. while cooling in ice The mixture is stirred at room temperature for 1 hour heated under reflux for 30 minutes the solvent is removed by distillation in vacuo The phases are separated the aqueous solution is again extracted with methylene chloride The combined organic phases are washed with water dried with sodium sulphate the methylene chloride is removed in vacuo The crystalline residue is recrystallized from cyclohexane