piperidine;hydrochloride

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

Procedure: A solution of 5.3 g of sodium cyanide in 20 ml of water is added dropwise at RT to a solution of 18.9 g of 1-benzylpiperid-4-one and 12.16 g of piperidine hydrochloride in 25 ml of MeOH and 25 ml of water and the mixture is stirred for 48 hours at RT. The precipitate formed is filtered off, washed with water and dried under vacuum to give 27 g of the expected product. The precipitate formed is filtered off washed with water dried under vacuum

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

Procedure: A solution of 5.3 g of sodium cyanide in 20 ml of water is added dropwise at RT to a solution of 18.9 g of 1-benzylpiperid-4-one and 12.16 g of piperidine hydrochloride in 25 ml of MeOH and 25 ml of water and the mixture is stirred for 48 hours at RT. The precipitate formed is wrung, washed with water and dried under vacuum to give 27 g of the expected product. The precipitate formed washed with water dried under vacuum

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Piperidine hydrochloride (3.648 g, 30 mmol) was stirred in a mixture of 4.0 mL of water and 4.146 g of ground potassium carbonate. This mixture was heated to 90° C. and cyclohexene oxide (1.01 mL, 10 mmol) was added. The resulting mixture was heated at 100° C. for 18 hours. The reaction was cooled then filtered to remove carbonate salts. The filter cake was washed with 25 mL of diethyl ether and 50 mL of ethyl acetate. The filtrate and washings were combined and washed with brine (2×20 mL), dried over magnesium sulfate, filtered, and evaporated to give 1.875 g (>100%) of the title compound which was used without further purification. 1H NMR consistent with desired product. The resulting mixture was heated at 100° C. for 18 hours The reaction was cooled then filtered to remove carbonate salts The filter cake was washed with 25 mL of diethyl ether and 50 mL of ethyl acetate washed with brine (2×20 mL) dried over magnesium sulfate filtered evaporated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Piperidine hydrochloride (3.648 g, 30 mmol) was stirred in a mixture of 4.0 mL of water and 4.146 g of ground potassium carbonate. This mixture was heated to 90° C. and cyclohexene oxide (1.01 mL, 10 mmol) was added. The resulting mixture was heated at 100° C. for 18 hours. The reaction was cooled then filtered to remove carbonate salts. The filter cake was washed with 25 mL of diethyl ether and 50 mL of ethyl acetate. The filtrate and washings were combined and washed with brine (2×20 mL), dried over magnesium sulfate, filtered, and evaporated to give 1.875 g (>100%) of the title compound which was used without further purification. 1H NMR consistent with desired product. The resulting mixture was heated at 100° C. for 18 hours The reaction was cooled then filtered to remove carbonate salts The filter cake was washed with 25 mL of diethyl ether and 50 mL of ethyl acetate washed with brine (2×20 mL) dried over magnesium sulfate filtered evaporated

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

Procedure: 15 ml. of piperidine are added at onee to 13 g. of 3-nitro-4-chloro-benzophenone under stirring. Due to the highly exothermic reaction the mixture warms to 98° to 100°C within 4 to 5 minutes, thereafter piperidine hydrochloride starts to separate from the homogeneous reaction mixture. The mixture is stirred for 10 minutes at 98° to 100°C, thereafter cooled, the product is then triturated with 30 ml. of n-hexane, and filtered. The crystalline substance is washed on the filter with 2×30 ml. of n-hexane, subjected to effective suction well, and suspended several times in distilled water to remove piperidine hydrochloride. The obtained product is dried until a constant weight is obtained. 15.5 g. of crystalline 3-nitro-4-piperidino-benzophenone are obtained; m.p.: 77°C. Due to the highly exothermic reaction the mixture to separate from the homogeneous reaction mixture cooled the product is then triturated with 30 ml of n-hexane, and filtered The crystalline substance is washed on the filter with 2×30 ml to remove piperidine hydrochloride The obtained product is dried until a constant weight is obtained

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

Procedure: A solution of 5.3 g of sodium cyanide in 20 ml of water is added dropwise at RT to a solution of 18.9 g of 1-benzylpiperid-4-one and 12.16 g of piperidine hydrochloride in 25 ml of MeOH and 25 ml of water and the mixture is stirred for 48 hours at RT. The precipitate formed is wrung, washed with water and dried under vacuum to give 27 g of the expected product. The precipitate formed washed with water dried under vacuum

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

Procedure: 12.5 Parts of 3-(2-chloroanilino)-5,5-dimethyl-2-cyclohexen-1-one is dissolved in 30 volume parts of methanol under warming and, then, to the resulting solution are added 4.5 parts of a 37 weight % aqueous solution of formaldehyde, 6.05 parts of piperidine hydrochloride and 2 drops of glacial acetic acid. The whole mixture is allowed to stand at room temperature for 1 hour, whereupon a yellow, clear solution is obtained. The methanol is distilled off under reduced pressure, and a small amount of isopropyl ether is added to the resulting residue, followed by cooling, whereupon colorless crystals separate. The crystals are collected by filtration and recrystallized from acetone. The procedure yields colorless prisms of 3-(2-chloroanilino)-5,5-dimethyl-2-piperidinomethyl-2-cyclohexen-1-one hydrochloride. Melting point: 105°-106°C. Elementary analysis: C20H28N2OCl2.1/2H2O Calcd. C, 61.21; H, 7.45; N, 7.14 Found C, 60.91; H, 7.60; N, 7.25. under warming whereupon a yellow, clear solution is obtained The methanol is distilled off under reduced pressure a small amount of isopropyl ether is added to the resulting residue by cooling, whereupon colorless crystals separate The crystals are collected by filtration recrystallized from acetone

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

Procedure: 12.5 Parts of 3-(2-chloroanilino)-5,5-dimethyl-2-cyclohexen-1-one is dissolved in 30 volume parts of methanol under warming and, then, to the resulting solution are added 4.5 parts of a 37 weight % aqueous solution of formaldehyde, 6.05 parts of piperidine hydrochloride and 2 drops of glacial acetic acid. The whole mixture is allowed to stand at room temperature for 1 hour, whereupon a yellow, clear solution is obtained. The methanol is distilled off under reduced pressure, and a small amount of isopropyl ether is added to the resulting residue, followed by cooling, whereupon colorless crystals separate. The crystals are collected by filtration and recrystallized from acetone. The procedure yields colorless prisms of 3-(2-chloroanilino)-5,5-dimethyl-2-piperidinomethyl-2-cyclohexen-1-one hydrochloride. Melting point: 105°-106°C. Elementary analysis: C20H28N2OCl2.1/2H2O Calcd. C, 61.21; H, 7.45; N, 7.14 Found C, 60.91; H, 7.60; N, 7.25. under warming whereupon a yellow, clear solution is obtained The methanol is distilled off under reduced pressure a small amount of isopropyl ether is added to the resulting residue by cooling, whereupon colorless crystals separate The crystals are collected by filtration recrystallized from acetone

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

Procedure: This Example illustrates the preparation of 7-tert-butyl-4-methyl-3-piperidinomethyl,1,2-dihydronaphthalene (Compound number 3 of Table I). Piperidine hydrochloride (12.6 g 0.103 mol), 6-tert-butyl-1,2,3,4-tetrahydronaphthalen-1-one (80.0 g, 0.04 mol) and paraformaldehyde (2.64 g, 0.088 mol) were refluxed in ethanol (200 ml) with concentrated hydrochloric acid (1 ml) as a catalyst for 48 hours. The reaction mixture was concentrated under reduced pressure and the residue dissolved in water then extracted with diethyl ether. The resulting aqueous solution was neutralized with sodium bicarbonate and extracted with diethyl ether (2×200 ml); the ethereal extracts were dried over magnesium sulphate and concentrated under reduced pressure to give 6-tert-butyl-2-piperidinomethyl-1,2,3,4-tetrahydronaphthalen-1-one (10.0 g 83% yield) melting at 47°-9°. The reaction mixture was concentrated under reduced pressure the residue dissolved in water then extracted with diethyl ether extracted with diethyl ether (2×200 ml) the ethereal extracts were dried over magnesium sulphate concentrated under reduced pressure

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

Procedure: This Example illustrates the preparation of 7-tert-butyl-4-methyl-3-piperidinomethyl,1,2-dihydronaphthalene (Compound number 3 of Table I). Piperidine hydrochloride (12.6 g 0.103 mol), 6-tert-butyl-1,2,3,4-tetrahydronaphthalen-1-one (80.0 g, 0.04 mol) and paraformaldehyde (2.64 g, 0.088 mol) were refluxed in ethanol (200 ml) with concentrated hydrochloric acid (1 ml) as a catalyst for 48 hours. The reaction mixture was concentrated under reduced pressure and the residue dissolved in water then extracted with diethyl ether. The resulting aqueous solution was neutralized with sodium bicarbonate and extracted with diethyl ether (2×200 ml); the ethereal extracts were dried over magnesium sulphate and concentrated under reduced pressure to give 6-tert-butyl-2-piperidinomethyl-1,2,3,4-tetrahydronaphthalen-1-one (10.0 g 83% yield) melting at 47°-9°. The reaction mixture was concentrated under reduced pressure the residue dissolved in water then extracted with diethyl ether extracted with diethyl ether (2×200 ml) the ethereal extracts were dried over magnesium sulphate concentrated under reduced pressure

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

Procedure: This Example illustrates the preparation of 6-tert-butyl-3-piperidinomethyl-1,2-dihydronaphthalene (Compound number 4 of Table I). Piperidine hydrochloride (8.9 g, 0.073 mol), 7-tert-butyl-1,2,3,4-tetrahydronaphthalen-1-one (7.0 g, 0.035 mol) and paraformaldehyde (2.2 g, 0.073 mol) were refluxed together in ethanol (150 ml) along with concentrated hydrochloric acid (1 ml) as a catalyst for 16 hours. The reaction mixture was concentrated under reduced pressure and the residue dissolved in water then extracted with diethyl ether. The resulting aqueous solution was neutralized with sodium bicarbonate and extracted with diethyl ether (2×200 ml); the ethereal extracts were dried over magnesium sulphate and concentrated under reduced pressure to give 7-tert-butyl-2-piperidinomethyl-1,2,3,4-tetrahydronaphthalen-1-one (4.5 g, 43% yield) as a buff coloured solid melting at 62°-3°. The 7-tert-butyl-2-piperidinomethyl-1,2,3,4-tetrahydronaphthalen-1-one (4.5 g, 0.015 mol) was dissolved in methanol (100 ml) and sodium borohydride (0.6 g, 0.016 mol) was added portionwise over 30 minutes at room temperature. It was stirred for 3 hours at room temperature then the methanol was evaporated under reduced pressure and the residue treated with water (100 ml) and extracted with ether (2×100 ml) which was washed with brine, dried over magnesium sulphate and evaporated under reduced pressure to give a viscous oil (4.0 g) which crystallised on standing. Separation by column chromatography on silica gel (Merck 60) using a gradient elution of petrol 60°-80° to ethyl acetate gave the alcohol as two isomers: The reaction mixture was concentrated under reduced pressure the residue dissolved in water then extracted with diethyl ether extracted with diethyl ether (2×200 ml) the ethereal extracts were dried over magnesium sulphate concentrated under reduced pressure

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

Procedure: A solution of 5.3 g of sodium cyanide in 20 ml of water is added dropwise at RT to a solution of 18.9 g of 1-benzylpiperid-4-one and 12.16 g of piperidine hydrochloride in 25 ml of MeOH and 25 ml of water and the mixture is stirred for 48 hours at RT. The precipitate formed is wrung, washed with water and dried under vacuum to give 27 g of the expected product. The precipitate formed washed with water dried under vacuum