1-benzyl-3-methylpiperidin-4-ol

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

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Subsequently, 3.13 g of the 1-benzyl-3-methyl-4-piperidone obtained above was dissolved in 6 ml of ether. The solution was added dropwise to a suspension of 0.44 g of lithium aluminum hydride in 25 ml of ether over 5 minutes while maintaining the temperature at 24°-27° C. Then, the mixture was stirred at 25° C. for 10 minutes, and, 5 ml of water was added thereto under ice-cooling. The mixture was extracted with 30 ml of ether four times. The ether layer was washed with water, dried over anhydrous sodium sulfate and concentrated to obtain 3.17 g of an oily matter of 1-benzyl-4-hydroxy-3-methylpiperidine. while maintaining the temperature at 24°-27° C under ice-cooling The mixture was extracted with 30 ml of ether four times The ether layer was washed with water dried over anhydrous sodium sulfate concentrated

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

Procedure: A solution (15 ml) of 3.98 g of 1-benzyl-3-methyl-4-piperidone in diethyl ether was added to a suspension (10 ml) of 0.78 g of aluminum lithium hydride in diethyl ether in an ice bath, and the solution was heated under ref lux for 3 hours. Water was added to the solution, and the solution was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous solution of hydrogen chloride. The solution was dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified with silica gel column chromatography, and from the fractions eluted with chloroform-methanol (19:1 v/v) was obtained 2.76 g of 1-benzyl-4-hydroxy-3-methylpiperidine, which was an oily product (yield: 69%). the solution was heated under ref lux for 3 hours the solution was extracted with ethyl acetate the organic layer was washed with saturated aqueous solution of hydrogen chloride The solution was dried with anhydrous sodium sulfate concentrated under reduced pressure The residue was purified with silica gel column chromatography from the fractions eluted with chloroform-methanol (19:1 v/v)

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

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

Procedure: To a cis/trans mixture of 1-benzyl-3-methyl-piperidin-4-ol (50 g, 243 mmol, prepared as described in Can. J. Chem. (1972) 50, 803) in THF is added triethylamine (51 ml, 365 mmol) followed by 2,2-dimethyl-propionyl chloride (45 ml, 365 mmol). The reaction is exothermic and a precipitate is formed. The mixture is heated under reflux for 18 hours, cooled, filtered and washed with ether. The organic layers are washed with 1N—NaOH and brine, dried and evaporated. The crude is purified by chromatography on silicagel using hexane and EtOAc (5%) to give pure trans-isomer as a colourless oil. a precipitate is formed The mixture is heated under reflux for 18 hours cooled filtered washed with ether The organic layers are washed with 1N—NaOH and brine dried evaporated The crude is purified by chromatography on silicagel to give pure trans-isomer as a colourless oil

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

Procedure: To a cis/trans mixture of 1-benzyl-3-methyl-piperidin-4-ol (50 g, 243 mmol, prepared as described in Can. J. Chem. (1972) 50, 803) in THF is added triethylamine (51 ml, 365 mmol) followed by 2,2-dimethyl-propionyl chloride (45 ml, 365 mmol). The reaction is exothermic and a precipitate is formed. The mixture is heated under reflux for 18 hours, cooled, filtered and washed with ether. The organic layers are washed with 1N-NaOH and brine, dried and evaporated. The crude is purified by chromatography on silicagel using hexane and EtOAc (5%) to give pure trans-isomer as a colourless oil. a precipitate is formed The mixture is heated under reflux for 18 hours cooled filtered washed with ether The organic layers are washed with 1N-NaOH and brine dried evaporated The crude is purified by chromatography on silicagel to give pure trans-isomer as a colourless oil

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

Procedure: Benzyl-3- methyl-piperidin-4-one (2.0 g, 10 mmol) was dissolved in MeOH (10 ml), cooled to 0° C. and sodium borohydride (0.2 g, 5 mmol) was added portionwise. The reaction was allowed to reach room temperature and stirred overnight after which time the solvent was removed under vacuum, the residue redissolved in CH2Cl2, washed with water, dried (Na2SO4) and concentrated to afford the title compound (2.1 g, quant), a 3:1 mixture of diasteriomers (trans:cis) as gum. MS: 206.2 (MH+). to reach room temperature was removed under vacuum the residue redissolved in CH2Cl2 washed with water dried (Na2SO4) concentrated

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

Procedure: Suspend lithium aluminum hydride (0.76 g, 20.0 mmol) in dry tetrahydrofuran (10 mL) and cool to 0° C. Add, dropwise with stirring, 1-benzyl-3-methyl-piperidin-4-one (4.06 g, 20.0 mmol) in tetrahydrofuran (20 mL). After 1 hr., quench with saturated potassium sodium tartrate solution. After 20 min., extract with ethyl acetate (2×100 mL), wash the combined organic layers with aqueous NaCl solution (100 mL), dry over sodium sulfate, filter, and concentrate to obtain the title compound (4.15 g, >100%). Mass spectrum (electrospray): m/z=206.1 (M+1). Add , quench with saturated potassium sodium tartrate solution After 20 min. extract with ethyl acetate (2×100 mL) wash the combined organic layers with aqueous NaCl solution (100 mL) dry over sodium sulfate filter concentrate

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Subsequently, 3.13 g of the 1-benzyl-3-methyl-4-piperidone obtained above was dissolved in 6 ml of ether. The solution was added dropwise to a suspension of 0.44 g of lithium aluminum hydride in 25 ml of ether over 5 minutes while maintaining the temperature at 24°-27° C. Then, the mixture was stirred at 25° C. for 10 minutes, and, 5 ml of water was added thereto under ice-cooling. The mixture was extracted with 30 ml of ether four times. The ether layer was washed with water, dried over anhydrous sodium sulfate and concentrated to obtain 3.17 g of an oily matter of 1-benzyl-4-hydroxy-3-methylpiperidine. while maintaining the temperature at 24°-27° C under ice-cooling The mixture was extracted with 30 ml of ether four times The ether layer was washed with water dried over anhydrous sodium sulfate concentrated

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

Procedure: A solution (15 ml) of 3.98 g of 1-benzyl-3-methyl-4-piperidone in diethyl ether was added to a suspension (10 ml) of 0.78 g of aluminum lithium hydride in diethyl ether in an ice bath, and the solution was heated under ref lux for 3 hours. Water was added to the solution, and the solution was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous solution of hydrogen chloride. The solution was dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified with silica gel column chromatography, and from the fractions eluted with chloroform-methanol (19:1 v/v) was obtained 2.76 g of 1-benzyl-4-hydroxy-3-methylpiperidine, which was an oily product (yield: 69%). the solution was heated under ref lux for 3 hours the solution was extracted with ethyl acetate the organic layer was washed with saturated aqueous solution of hydrogen chloride The solution was dried with anhydrous sodium sulfate concentrated under reduced pressure The residue was purified with silica gel column chromatography from the fractions eluted with chloroform-methanol (19:1 v/v)