2-[(4-chlorophenyl)methyl]pyrrolidine

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: Heat 1.05 g of 5-(4-chlorobenzyl)pyrrolidin-2-one and 0.2 g of lithium aluminum hydride under reflux for 20 hours in 20 ml of tetrahydrofuran. Effect decomposition of the reaction product by admixing it with ice water. Then add 5 ml of 6 N sodium hydroxide solution to the resulting admixture and extract the thus-prepared base with diethyl ether. After drying the ether extract over sodium sulfate, concentrate it to obtain 0.7 g of the title compound as an oil. Convert the oil into the corresponding hydrochloride with methanol/ethereal hydrochloric acid; yield: 580 mg; m.p. of the hydrochloride 189° to 192°. extract the thus-prepared base with diethyl ether After drying the ether extract over sodium sulfate concentrate it

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

Procedure: Add a solution of 37.6 g of dibenzoyl-L-tartaric acid in 250 ml of acetone to 19.57 g of 2-(4-chlorobenzyl)pyrrolidine dissolved in 200 ml of acetone. Allow the resulting reaction mixture to stand for 12 hours and then filter off the precipitated crystals (25.8 g); [α]58920 =-84.7° (25 mg/ml in methanol). Recrystallize from 75 ml methanol/100 ml acetone to obtain 15.43 g of (-)-2-(4-chlorobenzyl)pyrrolidine dibenzoyl tartrate (m.p. 178° to 179°); [α]58920 =-88° (25 mg/ml in methanol). Stir 14.85 g of this salt with sodium hydroxide solution/diethyl ether until two clear phases form. Collect the ether phase and dry it over sodium sulfate. Thereafter, concentrate the dried ether phase to obtain the title compound as a colorless oil (5.0 g). Treat the colorless oil with methanol/ethereal hydrochloric acid to convert it into 4.83 g of the corresponding hydrochloride (m.p. 216° to 218°); [α]58920 =-31.4° (25 mg/ml in methanol). the resulting reaction mixture filter off the precipitated crystals (25.8 g) [α]58920 =-84.7° (25 mg/ml in methanol) Recrystallize from 75 ml methanol/100 ml acetone

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

Procedure: Boil 4 g of 2-(4-chlorobenzyl)pyrrolidine, 6.8 g of ω-chloro-4-fluorobutyrophenone, 4.2 g of potassium carbonate and 20 ml of methyl ethyl ketone under reflux for 68 hours. After cooling the resulting reaction mixture to ambient temperature, add 50 ml of water and 50 ml of diethyl ether. Collect the ether phase and dry it over sodium sulfate. Concentrate the dried ether phase to a brown oil before distilling it under a high vacuum to obtain 2.0 g of the title compound as viscous light-brown oil of b.p. 188° to 192° at 0.02 mm of Hg. After cooling the resulting reaction mixture to ambient temperature Collect the ether phase dry it over sodium sulfate Concentrate the dried ether phase to a brown oil before distilling it under a high vacuum

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

Procedure: Boil 5 g of 2-(4-chlorobenzyl)pyrrolidine, 3.53 g of anhydrous potassium carbonate, 4.6 g of 1-bromohexane and 50 ml of ethyl methyl ketone under reflux for 18 hours. Work up according to the procedure o Example 67 to obtain 5.82 g (81% of theory) of the title compound as a colorless liquid of b.p. 110° to 112° at 0.005 mm of Hg.

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

Procedure: Boil 5 g of 2-(4-chlorobenzyl)pyrrolidine, 3.53 g of anhydrous potassium carbonate, 3.4 g of allyl bromide and 50 ml of ethyl methyl ketone under reflux for 1 hour. Evaporate off the solvent. Take up the residue with 50 ml of water and extract 3 times with, in each case, 30 ml of diethyl ether. Combine the ether phases and dry them over sodium sulfate. Distil off the solvent from the combined ether extract and distil the resulting residue under a vacuum to obtain 5.12 g (85% of theory) of the title compound (b.p. 84° to 87° at 0.005 mm of Hg). m.p. of the picrate (from ethanol): 115° to 117°. Evaporate off the solvent extract 3 times with, in each case, 30 ml of diethyl ether dry them over sodium sulfate Distil off the solvent from the combined ether extract distil the resulting residue under a vacuum

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

Procedure: Add (dropwise, at 0° to 8°) 5.2 g of cyclopropanecarboxylic acid chloride in 10 ml of dichloromethane to 10 g of 2-(4-chlorobenzyl)pyrrolidine and 6.2 g of triethylamine. Stir the thus-prepared reaction mixture for a further 2 hours at 0°. Add water thereto. Separate off the organic phase and extract it with dichloromethane. Combine the organic phases and wash them with dilute hydrochloric acid and sodium carbonate solution. Dry the washed material over sodium sulfate. Evaporate off the solvent from the dried material, and then distil the oily residue to obtain the title compound (8.85 g) in the form of oil (b.p. 135° to 137° at 0.005 mm Hg), which solidifies to a crystalline mass of m.p. 62° to 64°. the thus-prepared reaction mixture for a further 2 hours at 0° Separate off the organic phase extract it with dichloromethane wash them with dilute hydrochloric acid and sodium carbonate solution Dry the washed material over sodium sulfate Evaporate off the solvent from the dried material distil the oily residue