1,2,2,6,6-pentamethylpiperidin-4-one

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

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

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

Procedure: 1,2,2,6,6-Pentamethyl-piperidin-4-one (8.64 g, 50.00 mmol) and phenol (4.98 g, 53.00 mmol) were melted together at 60° C. in a 100 mL round bottomed flask after which 13.5 mL of concentrated hydrochloric acid was added dropwise. The yellow solution was stirred at 70° C. for 24 hours. The mixture was poured into a beaker containing ice. Ammonium hydroxide was added carefully while stirring until the pH reached 7˜8. The mixture was extracted with EtOAc five times. The organic phases were combined, dried (Na2SO4) and concentrated. The residue was purified by chromatography on a silica gel column, eluting with 7N NH3 in methanol/dichloromethane to give 4-(1,2,2,6,6-pentamethyl-1,2,3,6-tetrahydropyridin-4-yl)-phenol (4.11 g, 34%). The mixture was poured into a beaker containing ice while stirring until the pH The mixture was extracted with EtOAc five times dried (Na2SO4) concentrated The residue was purified by chromatography on a silica gel column eluting with 7N NH3 in methanol/dichloromethane

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

Procedure: To a stirred solution of 1,2,2,6,6-pentamethylpiperidin-4-one (1.5 g, 8.88 mmol) in diethyl ether (25 mL) at rt was added MeLi (1.6 M, 5.5 mL, 8.88 mmol) slowly. The resulting mixture was stirred at rt for 30 min before it was quenched with sat. NH4Cl (15 mL). The mixture was then partitioned between EtOAc (35 mL) and sat. NaHCO3 (25 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to give crude 1,2,2,4,6,6-hexamethylpiperidin-4-ol (1.51 g) as an oil. LC-MS (ESI) m/z 186 (M+H)+. was quenched with sat. NH4Cl (15 mL) The mixture was then partitioned between EtOAc (35 mL) and sat. NaHCO3 (25 mL) The organic layer was dried over Na2SO4 filtered concentrated under reduced pressure

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

Procedure: The procedure described in Preparation 1(a) was repeated, but using as starting materials 1,2,2,6,6-pentamethyl-4-piperidone and ammonia, to give the title compound, boiling at 76°-79.5° C./5 mmHg (667 Pascals).

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

Procedure: 1,2,2,6,6-Pentamethyl-piperidin-4-one (8.64 g, 50.00 mmol) and phenol (4.98 g, 53.00 mmol) were melted together at 60° C. in a 100 mL round bottomed flask after which 13.5 mL of concentrated hydrochloric acid was added dropwise. The yellow solution was stirred at 70° C. for 24 hours. The mixture was poured into a beaker containing ice. Ammonium hydroxide was added carefully while stirring until the pH reached 7˜8. The mixture was extracted with EtOAc five times. The organic phases were combined, dried (Na2SO4) and concentrated. The residue was purified by chromatography on a silica gel column, eluting with 7N NH3 in methanol/dichloromethane to give 4-(1,2,2,6,6-pentamethyl-1,2,3,6-tetrahydropyridin-4-yl)-phenol (4.11 g, 34%). The mixture was poured into a beaker containing ice while stirring until the pH The mixture was extracted with EtOAc five times dried (Na2SO4) concentrated The residue was purified by chromatography on a silica gel column eluting with 7N NH3 in methanol/dichloromethane

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: 1,2,2,6,6-Pentamethyl-piperidin-4-one oxime was prepared from 1,2,2,6,6-pentamethyl-piperidin-4-one and hydroxylamine hydrochloride using conditions of General Method 1. 1H NMR (250 MHz, CHLOROFORM-d) δ 2.52 (2H, s), 2.28 (3H, s), 2.21 (2H, s), 1.12 (6H, s), 1.11 (6H, s).

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

Procedure: 1,2,2,6,6-Pentamethyl-piperidin-4-one oxime was prepared from 1,2,2,6,6-pentamethyl-piperidin-4-one and hydroxylamine hydrochloride using conditions of General Method 1. 1H NMR (250 MHz, CHLOROFORM-d) δ 2.52 (2H, s), 2.28 (3H, s), 2.21 (2H, s), 1.12 (6H, s), 1.11 (6H, s).

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

Procedure: To a stirred solution of 1,2,2,6,6-pentamethylpiperidin-4-one (1.5 g, 8.88 mmol) in diethyl ether (25 mL) at rt was added MeLi (1.6 M, 5.5 mL, 8.88 mmol) slowly. The resulting mixture was stirred at rt for 30 min before it was quenched with sat. NH4Cl (15 mL). The mixture was then partitioned between EtOAc (35 mL) and sat. NaHCO3 (25 mL). The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure to give crude 1,2,2,4,6,6-hexamethylpiperidin-4-ol (1.51 g) as an oil. LC-MS (ESI) m/z 186 (M+H)+. was quenched with sat. NH4Cl (15 mL) The mixture was then partitioned between EtOAc (35 mL) and sat. NaHCO3 (25 mL) The organic layer was dried over Na2SO4 filtered concentrated under reduced pressure

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

Procedure: The procedure described in Preparation 1(a) was repeated, but using as starting materials 1,2,2,6,6-pentamethyl-4-piperidone and ammonia, to give the title compound, boiling at 76°-79.5° C./5 mmHg (667 Pascals).