1-benzyl-4-methylpiperidin-4-ol

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: 1-Benzyl-4-methylpiperidin-4-ol (4.81 g, 23.4 mmol, 1.00 equiv) was added to a suspension of AlCl3 (15.62 g, 117 mmol, 5.00 equiv) in benzene (100 mL) at room temperature under argon. The mixture was stirred at reflux for 24 hours, then cooled and poured cautiously into ice water (100 g of ice plus 50 mL of water). The aqueous phase was adjusted to pH 11-12 by addition of 6 N aqueous NaOH at 0° C., and extracted with EtOAc (3×100 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was purified by flash chromatography (SiO2, hexane-Et2O 19:1 to 9:1 followed by hexane-EtOAc 3:1) to give 3.23 g (52%) of brown oil, which was characterized spectroscopically. at reflux for 24 hours cooled extracted with EtOAc (3×100 mL) The combined organic solutions were dried over MgSO4 concentrated The residue was purified by flash chromatography (SiO2, hexane-Et2O 19:1 to 9:1 followed by hexane-EtOAc 3:1)

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

Procedure: To a solution of 1-benzyl-4-piperidone (5.00 mL, 27.0 mmol, 1.00 equiv, Aldrich) in anhydrous ether at —78° C. under argon was added methyllithium (1.4 M in Et2O, 54.0 mL, 53.9 mmol, 2.00 equiv). Stirring was continued at −78° C. for 1.5 hours. Ether (200 mL) and water (40 mL) were added, and the two phases were separated. The aqueous solution was extracted with Et2O (3×50 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was purified by flash chromatography (SiO2, EtOAc to EtOAc-MeOH 9:1) to give 4.81 g (87%) of colorless oil, which was characterized spectroscopically. the two phases were separated The aqueous solution was extracted with Et2O (3×50 mL) The combined organic solutions were dried over MgSO4 concentrated The residue was purified by flash chromatography (SiO2, EtOAc to EtOAc-MeOH 9:1)

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

Procedure: 1-Benzyl-4-methyl-piperidin-4-ol (4.81 g, 23.4 mmol, 1.00 equiv) was added to a suspension of AlCl3 (15.62 g, 117 mmol, 5.00 equiv) in benzene (100 mL) at room temperature under argon. The mixture was stirred at reflux for 24 hours, then cooled and poured cautiously into ice water (100 g of ice plus 50 mL of water). The aqueous phase was adjusted to pH 11-12 by addition of 6 N aqueous NaOH at 0° C., and extracted with EtOAc (3×100 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was purified by flash chromatography (SiO2, hexane-Et2O 19:1 to 9:1 followed by hexane-EtOAc 3:1) to give 3.23 g (52%) of brown oil, which was characterized, spectroscopically. at reflux for 24 hours cooled extracted with EtOAc (3×100 mL) The combined organic solutions were dried over MgSO4 concentrated The residue was purified by flash chromatography (SiO2, hexane-Et2O 19:1 to 9:1 followed by hexane-EtOAc 3:1)

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

Procedure: To a solution of 1-benzyl-4-piperidone (5.00 mL, 27.0 mmol, 1.00 equiv, Aldrich) in anhydrous ether at −78° C. under argon was added methyllithium (1.4 M in Et2O, 54.0 mL, 53.9 mmol, 2.00 equiv). Stirring was continued at −78° C. for 1.5 hours. Ether (200 mL) and water (40 mL) were added, and the two phases were separated. The aqueous solution was extracted with Et2O (3×50 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was purified by flash chromatography (SiO2, EtOAc to EtOAc-MeOH 9:1) to give 4.81 g (87%) of colorless oil, which was characterized spectroscopically. the two phases were separated The aqueous solution was extracted with Et2O (3×50 mL) The combined organic solutions were dried over MgSO4 concentrated The residue was purified by flash chromatography (SiO2, EtOAc to EtOAc-MeOH 9:1)

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

Procedure: 1-Benzyl-4-methylpiperidin-4-ol (4.81 g, 23.4 mmol, 1.00 equiv) was added to a suspension of AlCl3 (15.62 g, 117 mmol, 5.00 equiv) in benzene (100 mL) at room temperature under argon. The mixture was stirred at reflux for 24 hours, then cooled and poured cautiously into ice water (100 g of ice plus 50 mL of water). The aqueous phase was adjusted to pH 11-12 by addition of 6N aqueous NaOH at 0° C., and extracted with EtOAc (3×100 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was purified by flash chromatography (SiO2, hexane-Et2O 19:1 to 9:1 followed by hexane-EtOAc 3:1) to give 3.23 g (52%) of brown oil, which was characterized spectroscopically. at reflux for 24 hours cooled extracted with EtOAc (3×100 mL) The combined organic solutions were dried over MgSO4 concentrated The residue was purified by flash chromatography (SiO2, hexane-Et2O 19:1 to 9:1 followed by hexane-EtOAc 3:1)

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

Procedure: To a solution of 1-benzyl-4-piperidone (5.00 mL, 27.0 mmol, 1.00 equiv, Aldrich) in anhydrous ether at −78° C. under argon was added methyllithium (1.4M in Et2O, 54.0 mL, 53.9 mmol, 2.00 equiv). Stirring was continued at −78° C. for 1.5 hours. Ether (200 mL) and water (40 mL) were added, and the two phases were separated. The aqueous solution was extracted with Et2O (3×50 mL). The combined organic solutions were dried over MgSO4 and concentrated. The residue was purified by flash chromatography (SiO2, EtOAc to EtOAc-MeOH 9:1) to give 4.81 g (87%) of colorless oil, which was characterized spectroscopically. the two phases were separated The aqueous solution was extracted with Et2O (3×50 mL) The combined organic solutions were dried over MgSO4 concentrated The residue was purified by flash chromatography (SiO2, EtOAc to EtOAc-MeOH 9:1)