(1-Isopropylpiperidin-4-yl)methanol

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:

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 1-isopropylpiperidine-4-methanol (0.40 g, 2.5 mmol) and N-methylmorpholine (0.46 g, 3.8 mmol) in methylene chloride (20 mL) was treated with tetrapropylammonium perruthenate (0.089 g, 0.25 mmol). After 3 h, the mixture was concentrated and the residue purified by column chromatography (SiO2: 10% to 20% methanol:methylene chloride) affording 0.20 g (50%) of the title compound. the mixture was concentrated the residue purified by column chromatography (SiO2: 10% to 20% methanol:methylene chloride)

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

Procedure: A solution of ethyl 1-isopropylpiperidine-4-carboxylate (10.0 g, 50.2 mmol) in THF (250 mL) at 0° C. was treated with lithium aluminum hydride (2.1 g, 55 mmol). After 1 h, the mixture was treated with a saturated aqueous solution of sodium potassium tartrate, partitioned with EtOAc, and the aqueous layer washed with EtOAc (2×). The combined extracts were dried (Na2SO4), concentrated, and the residue purified by column chromatography (SiO2: 10% methanol:methylene chloride) affording 4.30 g (54%) of the title compound. partitioned with EtOAc the aqueous layer washed with EtOAc (2×) The combined extracts were dried (Na2SO4) concentrated the residue purified by column chromatography (SiO2: 10% methanol:methylene chloride)

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

Procedure: A solution of ethyl 1-isopropylpiperidine-4-carboxylate (10.0 g, 50.2 mmol) in THF (250 mL) at 0° C. was treated with lithium aluminum hydride (2.1 g, 55 mmol). After 1 h, the mixture was treated with a saturated aqueous solution of sodium potassium tartrate, partitioned with EtOAc, and the aqueous layer washed with EtOAc (2×). The combined extracts were dried (Na2SO4), concentrated, and the residue purified by column chromatography (SiO2: 10% methanol:methylene chloride) affording 4.30 g (54%) of the title compound. partitioned with EtOAc the aqueous layer washed with EtOAc (2×) The combined extracts were dried (Na2SO4) concentrated the residue purified by column chromatography (SiO2: 10% methanol:methylene chloride)

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Oxalyl chloride (3.15 ml) was dissolved in 30 ml of dichloromethane, a solution of 3.20 ml of dimethyl sulfoxide in 6 ml of dichloromethane was added thereto at −70° C., the mixture was stirred for 15 minutes, a solution of 2.93 g of (1-isopropyl-4-piperidyl)methanol in 15 ml of dichloromethane was added thereto at −70° C. and the mixture was stirred for 1 hour. After 12.5 ml of triethylamine were added at −70° C., the mixture was raised to room temperature, then water and a saturated aqueous solution of sodium hydrogen carbonate were added and the mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate, the solvent was evaporated in vacuo and ethyl acetate was added to the resulting residue. After removing the insoluble matter by filtration, the solvent was evaporated in vacuo to give 1.15 g of 1-isopropylpiperidine-4-carbaldehyde. This compound was used for the next reaction without purification. at −70° C. and the mixture was stirred for 1 hour the mixture was raised to room temperature the mixture was extracted with chloroform The organic layer was dried over anhydrous magnesium sulfate the solvent was evaporated in vacuo and ethyl acetate was added to the resulting residue After removing the insoluble matter by filtration the solvent was evaporated in vacuo

Conditions: temp:-50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Lithium aluminum hydride (500 mg) was suspended in 40 ml of tetrahydrofuran, a solution of 3.55 g of ethyl 1-isopropylpiperidine-4-carboxylate in 10 ml of tetrahydrofuran was added thereto at −50° C. and the mixture was stirred for 2.5 hours from under ice-cooling to at room temperature. To this were added 0.5 ml of water, 0.5 ml of a 2N aqueous solution of sodium hydroxide, 1.5 ml of water and anhydrous magnesium sulfate under ice-cooling, the resulting precipitate was removed by filtration and the solvent was evaporated in vacuo to give 2.96 g of (1-isopropyl-4-piperidyl)methanol. cooling to at room temperature cooling the resulting precipitate was removed by filtration the solvent was evaporated in vacuo

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

Procedure: Lithium aluminum hydride (1.10 g) is suspended in tetrahydrofuran (80 ml), and thereto is added a solution of ethyl 1-isopropylpiperidine-4-carboxylate (5.00 g) obtained in Reference Example 127 in tetrahydrofuran (30 ml) dropwise under ice-cooling. The reaction solution is stirred for 2 hours under the ice-cooling, and water (1.1 ml), 15% aqueous sodium hydroxide solution (1.1 ml) and water (3.3 ml) are added dropwise successively and stirred for additional 10 minutes. To the resulting reaction solution is added potassium carbonate, and the mixture is stirred for 20 minutes, and then the insoluble materials are removed by filtration. The filtrate is concentrated under reduced pressure, and then the resulting residue is purified by NH-silica gel column chromatography (eluent: chloroform/ethyl acetate=1/1) to give (1-isopropylpiperidin-4-yl)methanol (4.29 g). cooling cooling To the resulting reaction solution the mixture is stirred for 20 minutes the insoluble materials are removed by filtration The filtrate is concentrated under reduced pressure the resulting residue is purified by NH-silica gel column chromatography (eluent: chloroform/ethyl acetate=1/1)