2-(1-benzylpiperidin-4-yl)oxyethanol

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

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

Procedure: 32.4 g (0.2 mole) of octanoyl chloride were added dropwise at 20° C (cooling with an ice bath) to a solution of 47 g (0.2 mole) of 2-(1-benzyl-4-piperidyloxy)-ethanol and 20.2 g (0.2 mole) of triethylamine in 300 ml of benzene and after standing for 24 hours at room temperature, the precipitate was removed by vacuum filtration. The benzene filtrate was washed with aqueous sodium bicarbonate solution, then with water, dried and the benzene evaporated off. The residue was dissolved in 300 ml of absolute ethanol and the solution was reacted with hydrogen at 50° C in the presence of 4.5 g of 5% palladized charcoal until the theoretical amount of hydrogen was absorbed. The catalyst was filtered off and after evaporation of the ethanol, the residue was distilled to obtain 35.5 g (64% yield) of ethyl 2-(4-piperidyloxy)-octanoate as a clear oil boiling at 150°-156° C at 0.1 mm Hg and having a refractive index nd20 = 1.464. the precipitate was removed by vacuum filtration The benzene filtrate was washed with aqueous sodium bicarbonate solution with water, dried the benzene evaporated off The residue was dissolved in 300 ml of absolute ethanol the solution was reacted with hydrogen at 50° C in the presence of 4.5 g of 5% was absorbed The catalyst was filtered off after evaporation of the ethanol the residue was distilled

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

Procedure: 15.6 g (0.2 mole) of acetyl chloride were added dropwise while cooling at 20° C with an ice bath to a solution of 47 g (0.2 mole) of 2-(1-benzyl-4-piperidyloxy)-ethanol, prepared according to the step B of Example I, and 20.2 g (0.2 mole) of triethylamine in 300 ml of benzene and after standing for 48 hours at room temperature, the precipitate was removed by vacuum filtration. The benzene filtrate was washed with aqueous sodium bicarbonate solution, then water, dried and the benzene distilled off. The residue was distilled to obtain 36.5 g (66% yield) of ethyl 2-(1-benzyl-4-piperidyloxy)-acetate as a clear oil boiling at 160°-170° C at 0.1 mm Hg and having a refractive index nD20 = 1.512. prepared the precipitate was removed by vacuum filtration The benzene filtrate was washed with aqueous sodium bicarbonate solution water, dried the benzene distilled off The residue was distilled

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

Procedure: 106.8 g of (0.8 mole) of aluminum chloride were added to a 2 liter, 3-neck flask and then 800 ml of anhydrous ether were added thereto with strong cooling. The mixture was stirred for 30 minutes and then a suspension of 7.6 g (0.2 mole) of lithium aluminum hydride in 200 ml of ether was added thereto. The mixture was stirred for 30 minutes and then a solution of 93.2 g (0.4 mole) of 8-benzyl-1,4-dioxa-8-aza-spiro [4,5] decane in 400 ml of anhydrous ether was added thereto dropwise. After the addition, stirring was continued at room temperature for 2 hours and 1 liter of water was then slowly added with strong cooling. The mixture was made alkaline with 90 g of sodium hydroxide pellets and the ether phase was decanted off. The aqueous layer was extracted again with ether and the combined ether phases were dried and the ether removed by distillation. The residue was distilled to obtain 63 g (67% yield) of 2-[1-benzyl-4-piperidyloxy]-ethanol in the form of a clear oil boiling at 140° C at 0.1 mm Hg and having a refractive index nD20 = 1.633. was added The mixture was stirred for 30 minutes After the addition stirring was continued at room temperature for 2 hours the ether phase was decanted off The aqueous layer was extracted again with ether the combined ether phases were dried the ether removed by distillation The residue was distilled

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

Procedure: 32.4 g (0.2 mole) of octanoyl chloride were added dropwise at 20° C (cooling with an ice bath) to a solution of 47 g (0.2 mole) of 2-(1-benzyl-4-piperidyloxy)-ethanol and 20.2 g (0.2 mole) of triethylamine in 300 ml of benzene and after standing for 24 hours at room temperature, the precipitate was removed by vacuum filtration. The benzene filtrate was washed with aqueous sodium bicarbonate solution, then with water, dried and the benzene evaporated off. The residue was dissolved in 300 ml of absolute ethanol and the solution was reacted with hydrogen at 50° C in the presence of 4.5 g of 5% palladized charcoal until the theoretical amount of hydrogen was absorbed. The catalyst was filtered off and after evaporation of the ethanol, the residue was distilled to obtain 35.5 g (64% yield) of ethyl 2-(4-piperidyloxy)-octanoate as a clear oil boiling at 150°-156° C at 0.1 mm Hg and having a refractive index nd20 = 1.464. the precipitate was removed by vacuum filtration The benzene filtrate was washed with aqueous sodium bicarbonate solution with water, dried the benzene evaporated off The residue was dissolved in 300 ml of absolute ethanol the solution was reacted with hydrogen at 50° C in the presence of 4.5 g of 5% was absorbed The catalyst was filtered off after evaporation of the ethanol the residue was distilled

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

Procedure: 32.4 g (0.2 mole) of octanoyl chloride were added dropwise at 20° C (cooling with an ice bath) to a solution of 47 g (0.2 mole) of 2-(1-benzyl-4-piperidyloxy)-ethanol and 20.2 g (0.2 mole) of triethylamine in 300 ml of benzene and after standing for 24 hours at room temperature, the precipitate was removed by vacuum filtration. The benzene filtrate was washed with aqueous sodium bicarbonate solution, then with water, dried and the benzene evaporated off. The residue was dissolved in 300 ml of absolute ethanol and the solution was reacted with hydrogen at 50° C in the presence of 4.5 g of 5% palladized charcoal until the theoretical amount of hydrogen was absorbed. The catalyst was filtered off and after evaporation of the ethanol, the residue was distilled to obtain 35.5 g (64% yield) of ethyl 2-(4-piperidyloxy)-octanoate as a clear oil boiling at 150°-156° C at 0.1 mm Hg and having a refractive index nd20 = 1.464. the precipitate was removed by vacuum filtration The benzene filtrate was washed with aqueous sodium bicarbonate solution with water, dried the benzene evaporated off The residue was dissolved in 300 ml of absolute ethanol the solution was reacted with hydrogen at 50° C in the presence of 4.5 g of 5% was absorbed The catalyst was filtered off after evaporation of the ethanol the residue was distilled

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

Procedure: 15.6 g (0.2 mole) of acetyl chloride were added dropwise while cooling at 20° C with an ice bath to a solution of 47 g (0.2 mole) of 2-(1-benzyl-4-piperidyloxy)-ethanol, prepared according to the step B of Example I, and 20.2 g (0.2 mole) of triethylamine in 300 ml of benzene and after standing for 48 hours at room temperature, the precipitate was removed by vacuum filtration. The benzene filtrate was washed with aqueous sodium bicarbonate solution, then water, dried and the benzene distilled off. The residue was distilled to obtain 36.5 g (66% yield) of ethyl 2-(1-benzyl-4-piperidyloxy)-acetate as a clear oil boiling at 160°-170° C at 0.1 mm Hg and having a refractive index nD20 = 1.512. prepared the precipitate was removed by vacuum filtration The benzene filtrate was washed with aqueous sodium bicarbonate solution water, dried the benzene distilled off The residue was distilled

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

Procedure: 15.6 g (0.2 mole) of acetyl chloride were added dropwise while cooling at 20° C with an ice bath to a solution of 47 g (0.2 mole) of 2-(1-benzyl-4-piperidyloxy)-ethanol, prepared according to the step B of Example I, and 20.2 g (0.2 mole) of triethylamine in 300 ml of benzene and after standing for 48 hours at room temperature, the precipitate was removed by vacuum filtration. The benzene filtrate was washed with aqueous sodium bicarbonate solution, then water, dried and the benzene distilled off. The residue was distilled to obtain 36.5 g (66% yield) of ethyl 2-(1-benzyl-4-piperidyloxy)-acetate as a clear oil boiling at 160°-170° C at 0.1 mm Hg and having a refractive index nD20 = 1.512. prepared the precipitate was removed by vacuum filtration The benzene filtrate was washed with aqueous sodium bicarbonate solution water, dried the benzene distilled off The residue was distilled

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

Procedure: 106.8 g of (0.8 mole) of aluminum chloride were added to a 2 liter, 3-neck flask and then 800 ml of anhydrous ether were added thereto with strong cooling. The mixture was stirred for 30 minutes and then a suspension of 7.6 g (0.2 mole) of lithium aluminum hydride in 200 ml of ether was added thereto. The mixture was stirred for 30 minutes and then a solution of 93.2 g (0.4 mole) of 8-benzyl-1,4-dioxa-8-aza-spiro [4,5] decane in 400 ml of anhydrous ether was added thereto dropwise. After the addition, stirring was continued at room temperature for 2 hours and 1 liter of water was then slowly added with strong cooling. The mixture was made alkaline with 90 g of sodium hydroxide pellets and the ether phase was decanted off. The aqueous layer was extracted again with ether and the combined ether phases were dried and the ether removed by distillation. The residue was distilled to obtain 63 g (67% yield) of 2-[1-benzyl-4-piperidyloxy]-ethanol in the form of a clear oil boiling at 140° C at 0.1 mm Hg and having a refractive index nD20 = 1.633. was added The mixture was stirred for 30 minutes After the addition stirring was continued at room temperature for 2 hours the ether phase was decanted off The aqueous layer was extracted again with ether the combined ether phases were dried the ether removed by distillation The residue was distilled

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

Procedure: 106.8 g of (0.8 mole) of aluminum chloride were added to a 2 liter, 3-neck flask and then 800 ml of anhydrous ether were added thereto with strong cooling. The mixture was stirred for 30 minutes and then a suspension of 7.6 g (0.2 mole) of lithium aluminum hydride in 200 ml of ether was added thereto. The mixture was stirred for 30 minutes and then a solution of 93.2 g (0.4 mole) of 8-benzyl-1,4-dioxa-8-aza-spiro [4,5] decane in 400 ml of anhydrous ether was added thereto dropwise. After the addition, stirring was continued at room temperature for 2 hours and 1 liter of water was then slowly added with strong cooling. The mixture was made alkaline with 90 g of sodium hydroxide pellets and the ether phase was decanted off. The aqueous layer was extracted again with ether and the combined ether phases were dried and the ether removed by distillation. The residue was distilled to obtain 63 g (67% yield) of 2-[1-benzyl-4-piperidyloxy]-ethanol in the form of a clear oil boiling at 140° C at 0.1 mm Hg and having a refractive index nD20 = 1.633. was added The mixture was stirred for 30 minutes After the addition stirring was continued at room temperature for 2 hours the ether phase was decanted off The aqueous layer was extracted again with ether the combined ether phases were dried the ether removed by distillation The residue was distilled

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

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

Procedure: A solution of (B) (12 g) in ethanol (200 ml) was neutralized with an ethanolic solution of hydrogen bromide and hydrogenated in the presence of 10% palladium on carbon (2.4 g). After 5 hours the uptake of hydrogen ceased and the catalyst was removed by filtration. The filtrate was taken to dryness in vacuo to give (C) as a semicrystalline solid. the catalyst was removed by filtration