4-(4-chlorophenyl)-3,3-dimethylpiperidin-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: 4-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidine-1-carboxylic acid tert-butyl ester (0.25 g, 0.73 mmol) was dissolved in 4M HCl/Dioxane (2 mL, 8 mmol). The solution was stirred at room temperature for about 4 hours. The solvent was removed in vacuo. The residue was quenched with aqueous sodium hydroxide, extracted with ethyl acetate, and the organic layers were dried over sodium sulfate and evaporated in vacuo to yield the title compound as a yellow solid. The mixture was carried on to the next step without further purification. The solvent was removed in vacuo The residue was quenched with aqueous sodium hydroxide extracted with ethyl acetate the organic layers were dried over sodium sulfate evaporated in vacuo

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

Procedure: 4-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidine-1-carboxylic acid tert-butyl ester (0.25 g, 0.73 mmol) was dissolved in 4M HCl/Dioxane (2 mL, 8 mmol). The solution was stirred at room temperature for about 4 hours. The solvent was removed in vacuo. The residue was quenched with aqueous sodium hydroxide, extracted with ethyl acetate, and the organic layers were dried over sodium sulfate and evaporated in vacuo to yield the title compound as a yellow solid. The mixture was carried on to the next step without further purification. The solvent was removed in vacuo The residue was quenched with aqueous sodium hydroxide extracted with ethyl acetate the organic layers were dried over sodium sulfate evaporated in vacuo

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

Procedure: A suspension of 4-(4-chlorophenyl)-3,3-dimethylpiperidin-4-ol (540 mg, 2.252 mmol) and benzaldehyde (0.274 mL, 2.70 mmol) in methylene chloride (15 mL) was treated with sodium triacetoxyborohydride (716 mg, 3.38 mmol), and the mixture was stirred overnight at room temperature. The mixture was concentrated in-vacuo. The residue was taken up in ethyl acetate, washed 3× with 1 N NaOH, once with brine, dried over sodium sulfate, and concentrated in-vacuo to yield the title compound (696 mg, 2.110 mmol, 94% yield) as a colorless oil. MS (ESI+)=330.14, (M+H)+. The mixture was concentrated in-vacuo washed 3× with 1 N NaOH once with brine, dried over sodium sulfate concentrated in-vacuo

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

Procedure: A suspension of 4-(4-chlorophenyl)-3,3-dimethylpiperidin-4-ol (540 mg, 2.252 mmol) and benzaldehyde (0.274 mL, 2.70 mmol) in methylene chloride (15 mL) was treated with sodium triacetoxyborohydride (716 mg, 3.38 mmol), and the mixture was stirred overnight at room temperature. The mixture was concentrated in-vacuo. The residue was taken up in ethyl acetate, washed 3× with 1 N NaOH, once with brine, dried over sodium sulfate, and concentrated in-vacuo to yield the title compound (696 mg, 2.110 mmol, 94% yield) as a colorless oil. MS (ESI+)=330.14, (M+H)+. The mixture was concentrated in-vacuo washed 3× with 1 N NaOH once with brine, dried over sodium sulfate concentrated in-vacuo

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

Procedure: To a cooled (0° C.) solution of 4-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidine-1-carboxylic acid tert-butyl ester (10.42 g, 30.7 mmol) in methylene chloride (300 mL) was slowly added trifluoroacetic acid (60 mL) over 1.25 hours. The resulting yellow solution was stirred at 0° C. for an additional 1.5 hours. The mixture was concentrated under reduced pressure and the residue dissolved in ethyl acetate (1.2 L), and washed with aqueous sodium hydroxide (1 N, 150 mL). The aqueous layer was extracted with additional ethyl acetate (200 mL) and the combined extracts were washed with brine, dried over sodium sulfate, filtered and concentrated. The resulting solid residue was triturated with ether to afford 4-(4-Chloro-phenyl)-3,3-dimethyl-piperidin-4-ol as an off-white solid. over 1.25 hours The mixture was concentrated under reduced pressure the residue dissolved in ethyl acetate (1.2 L) washed with aqueous sodium hydroxide (1 N, 150 mL) The aqueous layer was extracted with additional ethyl acetate (200 mL) the combined extracts were washed with brine dried over sodium sulfate filtered concentrated The resulting solid residue was triturated with ether

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

Procedure: 4-(4-Chloro-phenyl)-4-hydroxy-3,3-dimethyl-piperidine-1-carboxylic acid tert-butyl ester (0.25 g, 0.73 mmol) was dissolved in 4M HCl/Dioxane (2 mL, 8 mmol). The solution was stirred at room temperature for about 4 hours. The solvent was removed in vacuo. The residue was quenched with aqueous sodium hydroxide, extracted with ethyl acetate, and the organic layers were dried over sodium sulfate and evaporated in vacuo to yield the title compound as a yellow solid. The mixture was carried on to the next step without further purification. The solvent was removed in vacuo The residue was quenched with aqueous sodium hydroxide extracted with ethyl acetate the organic layers were dried over sodium sulfate evaporated in vacuo