3,3-dimethylpiperidin-4-one

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Benzyl-3,3-dimethyl-4-piperidone 275 g (1.26 mol) prepared as per procedure described in U.S. Pat. No. 5,846,980, was dissolved in 1.0 L. methanol. The solution was transferred to a Parr reactor after adding 10% palladium on carbon (25 g). The reaction mixture was stirred under 300 psi hydrogen pressure at 60° C. until chromatography showed complete conversion. The reaction mixture was filtered and the residue washed with methanol (200 ml). The filtrate was concentrated to dryness to afford 3,3-dimethyl-4-piperidone (158 g) which was used as such for the preparation of either 4-benzyloxycarbonylamino-3,3-dimethylpiperidine or 4-t-butyloxycarbonylamino-3,3-dimethylpiperidine. 5,846,980, was dissolved in 1.0 L The reaction mixture was filtered the residue washed with methanol (200 ml) The filtrate was concentrated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Benzyl-3,3-dimethyl-4-piperidone 275 g (1.26 mol), was dissolved in 1.0 L. methanol. The solution was transferred to a Parr reactor after adding 10% palladium on carbon (25 g). The reaction mixture was stirred under 300 psi hydrogen pressure at 60° C. until chromatography showed complete conversion. The reaction mixture was filtered and the residue washed with methanol (200 ml). The filtrate was concentrated to dryness to afford 3,3-dimethyl-4-piperidone (158 g) which was used as such for the preparation of either 4-benzyloxycarbonylamino-3,3-dimethylpiperidine or 4-t-butyloxycarbonylamino-3,3-dimethylpiperidine. The reaction mixture was filtered the residue washed with methanol (200 ml) The filtrate was concentrated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Benzyl-3,3-dimethyl-4-piperidone 275 g (1.26 mol), was dissolved in 1.0 L. methanol. The solution was transferred to a Parr reactor after adding 10% palladium on carbon (25 g). The reaction mixture was stirred under 300 psi hydrogen pressure at 60° C. until chromatography showed complete conversion. The reaction mixture was filtered and the residue washed with methanol (200 ml). The filtrate was concentrated to dryness to afford 3,3-dimethyl-4-piperidone (158 g) which was used as such for the preparation of either 4-benzyloxycarbonylamino-3,3-dimethylpiperidine or 4-t-butyloxycarbonylamino-3,3-dimethylpiperidine. The reaction mixture was filtered the residue washed with methanol (200 ml) The filtrate was concentrated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The 3,3-dimethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester thus prepared (450 mg, 1.97 mmol) was dissolved in methylene chloride (10 mL). Trifluoroacetic acid was added (305 uL) and the resulting solution stirred at room temperature 2 h. Additional trifluoroacetic acid was added (300 uL) and the reaction stirred at room temperature 3 days. The pale yellow solution was concentrated to afford an oily residue, which was triturated with ether. The solids were collected by suction filtration and dried in vacuo. 3,3-Dimethyl-piperidin-4-one was isolated and used as its trifluoroacetic acid salt (381 mg, 80%). 1H-NMR (d6-DMSO, 300 MHz) δ 3.44-3.33 (m, 4H), 2.63-2.57 (m, 2H), 1.11 (s, 6H). the reaction stirred at room temperature 3 days The pale yellow solution was concentrated to afford an oily residue, which was triturated with ether The solids were collected by suction filtration dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The 3,3-dimethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester thus prepared (450 mg, 1.97 mmol) was dissolved in methylene chloride (10 mL). Trifluoroacetic acid was added (305 uL) and the resulting solution stirred at room temperature 2 h. Additional trifluoroacetic acid was added (300 uL) and the reaction stirred at room temperature 3 days. The pale yellow solution was concentrated to afford an oily residue, which was triturated with ether. The solids were collected by suction filtration and dried in vacuo. 3,3-Dimethyl-piperidin-4-one was isolated and used as its trifluoroacetic acid salt (381 mg, 80%). 1H-NMR (d6-DMSO, 300 MHz) δ 3.44-3.33 (m, 4H), 2.63-2.57 (m, 2H), 1.11 (s, 6H). the reaction stirred at room temperature 3 days The pale yellow solution was concentrated to afford an oily residue, which was triturated with ether The solids were collected by suction filtration dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The 3,3-dimethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester thus prepared (450 mg, 1.97 mmol) was dissolved in methylene chloride (10 mL). Trifluoroacetic acid was added (305 uL) and the resulting solution stirred at room temperature 2 h. Additional trifluoroacetic acid was added (300 uL) and the reaction stirred at room temperature 3 days. The pale yellow solution was concentrated to afford an oily residue, which was triturated with ether. The solids were collected by suction filtration and dried in vacuo. 3,3-Dimethyl-piperidin-4-one was isolated and used as its trifluoroacetic acid salt (381 mg, 80%). the reaction stirred at room temperature 3 days The pale yellow solution was concentrated to afford an oily residue, which was triturated with ether The solids were collected by suction filtration dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The 3,3-dimethyl-4-oxo-piperidine-1-carboxylic acid tert-butyl ester thus prepared (450 mg, 1.97 mmol) was dissolved in methylene chloride (10 mL). Trifluoroacetic acid was added (305 uL) and the resulting solution stirred at room temperature 2 h. Additional trifluoroacetic acid was added (300 uL) and the reaction stirred at room temperature 3 days. The pale yellow solution was concentrated to afford an oily residue, which was triturated with ether. The solids were collected by suction filtration and dried in vacuo. 3,3-Dimethyl-piperidin-4-one was isolated and used as its trifluoroacetic acid salt (381 mg, 80%). the reaction stirred at room temperature 3 days The pale yellow solution was concentrated to afford an oily residue, which was triturated with ether The solids were collected by suction filtration dried in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Benzyl-3,3-dimethyl-4-piperidone 275 g (1.26 mol), was dissolved in 1.0 L. methanol. The solution was transferred to a Parr reactor after adding 10% palladium on carbon (25 g). The reaction mixture was stirred under 300 psi hydrogen pressure at 60° C. until chromatography showed complete conversion. The reaction mixture was filtered and the residue washed with methanol (200 ml). The filtrate was concentrated to dryness to afford 3,3-dimethyl-4-piperidone (158 g) which was used as such for the preparation of either 4-benzyloxycarbonylamino-3,3-dimethylpiperidine or 4-t-butyloxycarbonylamino-3,3-dimethylpiperidine. The reaction mixture was filtered the residue washed with methanol (200 ml) The filtrate was concentrated to dryness

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Fluoro-2-methoxy-1-nitrobenzene (1.550 g, 9.06 mmol), 3,3-dimethylpiperidin-4-one (INTERMEDIATE 38) (2.17 g, 9.06 mmol, TFA salt), and potassium carbonate (2.504 g, 18.12 mmol) in DMF (20 ml) were heated at 70° C. overnight. The reaction mixture was concentrated in vacuo to remove the solvent. The residue was partitioned between CH2Cl2 (100 mL) and water (30 mL). The organic phase was dried over MgSO4 and concentrated in vacuo. The residue was purified using silica gel column (50%-100% CH2Cl2/Hexane) to obtain the title product (1.100 g, 43.6%). The reaction mixture was concentrated in vacuo to remove the solvent The residue was partitioned between CH2Cl2 (100 mL) and water (30 mL) The organic phase was dried over MgSO4 concentrated in vacuo The residue was purified

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Trifluoroactic acid (4 mL, 51.92 mmol) was added to a solution of tert-butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate (2.0588 g, 9.06 mmol) in dichloromethane (12 mL). The reaction was stirred at RT for 2 h and the solution was concentrated to remove the solvent. The residue as the product was directly used in the next step without further purification. m/z 128. the solution was concentrated to remove the solvent The residue as the product was directly used in the next step without further purification