托品酮

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 500-mL Parr hydrogenation vessel was purged with nitrogen and charged with platinum (IV) oxide (1.28 g, 5.64 mmol), 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one oxime (4.00 g, 26.0 mmol), acetic acid (11 mL) and ethanol (110 mL). The bottle was evacuated, charged with hydrogen gas to a pressure of 50 psi and shaken for 24 h on a Parr hydrogenation apparatus. The hydrogen was then evacuated and nitrogen charged to the bottle. The reaction mixture was then mixed with Celite 521 (5.0 g), filtered, and the filtrate evaporated to a solid residue. This residue was dissolved in methanol (100 mL) and this solution treated with sodium carbonate (10 g). The resulting suspension was added diethyl ether (50 mL) and filtered. Evaporation of the filtrate to dryness afforded 3.64 g (100%) of 8-methyl-8-azabicyclo[3.2.1]oct-3-ylamine as a white solid: 1H NMR (300 MHz, CD3OD) δ 5.18 (br s, 2H), 3.35 (br s, 2H), 3.21 (t, J=6.6 Hz, 1H), 2.40 (s, 3H), 2.26-2.00 (m, 6H), 1.68-1.58 (m, 2H). A 500-mL Parr hydrogenation vessel was purged with nitrogen The bottle was evacuated charged with hydrogen gas to a pressure of 50 psi The hydrogen was then evacuated nitrogen charged to the bottle The reaction mixture was then mixed with Celite 521 (5.0 g) filtered the filtrate evaporated to a solid residue This residue was dissolved in methanol (100 mL) this solution treated with sodium carbonate (10 g) The resulting suspension was added diethyl ether (50 mL) filtered Evaporation of the filtrate to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer was charged with 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one (5.00 g, 35.9 mmol), hydroxylamine hydrochloride (7.08 g, 102 mmol) sodium acetate (39.0 g, 476 mmol) and ethanol (45 mL). After stirring at ambient temperature for 4 h, the reaction mixture was evaporated to a solid residue. This residue was triturated with ethyl acetate (200 mL) and filtered. Evaporation of the filtrate to dryness gave 5.08 g (93% yield) of 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one oxime as a white solid: mp 140-142° C.; 1H NMR (300 MHz, CD3OD) δ 3.76 (m, 2H), 3.33-3.23 (m, 2H), 2.75 (m, 1H), 2.69 (s, 3H), 2.46-2.14 (m, 4H), 1.88-1.66 (m, 2H); MS (APCI) m/z 155 [M+H]+. A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer the reaction mixture was evaporated to a solid residue This residue was triturated with ethyl acetate (200 mL) filtered Evaporation of the filtrate to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer was charged with 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one (5.00 g, 35.9 mmol), hydroxylamine hydrochloride (7.08 g, 102 mmol) sodium acetate (39.0 g, 476 mmol) and ethanol (45 mL). After stirring at ambient temperature for 4 h, the reaction mixture was evaporated to a solid residue. This residue was triturated with ethyl acetate (200 mL) and filtered. Evaporation of the filtrate to dryness gave 5.08 g (93% yield) of 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one oxime as a white solid: mp 140-142° C.; 1H NMR (300 MHz, CD3OD) δ 3.76 (m, 2H), 3.33-3.23 (m, 2H), 2.75 (m, 1H), 2.69 (s, 3H), 2.46-2.14 (m, 4H), 1.88-1.66 (m, 2H); MS (APCI) m/z 155 [M+H]+. A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer the reaction mixture was evaporated to a solid residue This residue was triturated with ethyl acetate (200 mL) filtered Evaporation of the filtrate to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 500-mL Parr hydrogenation vessel was purged with nitrogen and charged with platinum (IV) oxide (1.28 g, 5.64 mmol), 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one oxime (4.00 g, 26.0 mmol), acetic acid (11 mL) and ethanol (110 mL). The bottle was evacuated, charged with hydrogen gas to a pressure of 50 psi and shaken for 24 h on a Parr hydrogenation apparatus. The hydrogen was then evacuated and nitrogen charged to the bottle. The reaction mixture was then mixed with Celite 521 (5.0 g), filtered, and the filtrate evaporated to a solid residue. This residue was dissolved in methanol (100 mL) and this solution treated with sodium carbonate (10 g). The resulting suspension was added diethyl ether (50 mL) and filtered. Evaporation of the filtrate to dryness afforded 3.64 g (100%) of 8-methyl-8-azabicyclo[3.2.1]oct-3-ylamine as a white solid: 1H NMR (300 MHz, CD3OD) δ 5.18 (br s, 2H), 3.35 (br s, 2H), 3.21 (t, J=6.6 Hz, 1H), 2.40 (s, 3H), 2.26-2.00 (m, 6H), 1.68-1.58 (m, 2H). A 500-mL Parr hydrogenation vessel was purged with nitrogen The bottle was evacuated charged with hydrogen gas to a pressure of 50 psi The hydrogen was then evacuated nitrogen charged to the bottle The reaction mixture was then mixed with Celite 521 (5.0 g) filtered the filtrate evaporated to a solid residue This residue was dissolved in methanol (100 mL) this solution treated with sodium carbonate (10 g) The resulting suspension was added diethyl ether (50 mL) filtered Evaporation of the filtrate to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer was charged with 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one (5.00 g, 35.9 mmol), hydroxylamine hydrochloride (7.08 g, 102 mmol) sodium acetate (39.0 g, 476 mmol) and ethanol (45 mL). After stirring at ambient temperature for 4 h, the reaction mixture was evaporated to a solid residue. This residue was triturated with ethyl acetate (200 mL) and filtered. Evaporation of the filtrate to dryness gave 5.08 g (93% yield) of 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one oxime as a white solid: mp 140-142° C.; 1H NMR (300 MHz, CD3OD) δ 3.76 (m, 2H), 3.33-3.23 (m, 2H), 2.75 (m, 1H), 2.69 (s, 3H), 2.46-2.14 (m, 4H), 1.88-1.66 (m, 2H); MS (APCI) m/z 155 [M+H]+. A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer the reaction mixture was evaporated to a solid residue This residue was triturated with ethyl acetate (200 mL) filtered Evaporation of the filtrate to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer was charged with 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one (5.00 g, 35.9 mmol), hydroxylamine hydrochloride (7.08 g, 102 mmol) sodium acetate (39.0 g, 476 mmol) and ethanol (45 mL). After stirring at ambient temperature for 4 h, the reaction mixture was evaporated to a solid residue. This residue was triturated with ethyl acetate (200 mL) and filtered. Evaporation of the filtrate to dryness gave 5.08 g (93% yield) of 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one oxime as a white solid: mp 140-142° C.; 1H NMR (300 MHz, CD3OD) δ 3.76 (m, 2H), 3.33-3.23 (m, 2H), 2.75 (m, 1H), 2.69 (s, 3H), 2.46-2.14 (m, 4H), 1.88-1.66 (m, 2H); MS (APCI) m/z 155 [M+H]+. A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer the reaction mixture was evaporated to a solid residue This residue was triturated with ethyl acetate (200 mL) filtered Evaporation of the filtrate to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 500-mL Parr hydrogenation vessel was purged with nitrogen and charged with platinum (IV) oxide (1.28 g, 5.64 mmol), 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one oxime (4.00 g, 26.0 mmol), acetic acid (11 mL) and ethanol (110 mL). The bottle was evacuated, charged with hydrogen gas to a pressure of 50 psi and shaken for 24 h on a Parr hydrogenation apparatus. The hydrogen was then evacuated and nitrogen charged to the bottle. The reaction mixture was then mixed with Celite 521 (5.0 g), filtered, and the filtrate evaporated to a solid residue. This residue was dissolved in methanol (100 mL) and this solution treated with sodium carbonate (10 g). The resulting suspension was added diethyl ether (50 mL) and filtered. Evaporation of the filtrate to dryness afforded 3.64 g (100%) of 8-methyl-8-azabicyclo[3.2.1]oct-3-ylamine as a white solid: 1H NMR (300 MHz, CD3OD) δ 5.18 (br s, 2H), 3.35 (br s, 2H), 3.21 (t, J=6.6 Hz, 1H), 2.40 (s, 3H), 2.26-2.00 (m, 6H), 1.68-1.58 (m, 2H). A 500-mL Parr hydrogenation vessel was purged with nitrogen The bottle was evacuated charged with hydrogen gas to a pressure of 50 psi The hydrogen was then evacuated nitrogen charged to the bottle The reaction mixture was then mixed with Celite 521 (5.0 g) filtered the filtrate evaporated to a solid residue This residue was dissolved in methanol (100 mL) this solution treated with sodium carbonate (10 g) The resulting suspension was added diethyl ether (50 mL) filtered Evaporation of the filtrate to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer was charged with 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one (5.00 g, 35.9 mmol), hydroxylamine hydrochloride (7.08 g, 102 mmol) sodium acetate (39.0 g, 476 mmol) and ethanol (45 mL). After stirring at ambient temperature for 4 h, the reaction mixture was evaporated to a solid residue. This residue was triturated with ethyl acetate (200 mL) and filtered. Evaporation of the filtrate to dryness gave 5.08 g (93% yield) of 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one oxime as a white solid: mp 140-142° C.; 1H NMR (300 MHz, CD3OD) δ 3.76 (m, 2H), 3.33-3.23 (m, 2H), 2.75 (m, 1H), 2.69 (s, 3H), 2.46-2.14 (m, 4H), 1.88-1.66 (m, 2H); MS (APCI) m/z 155 [M+H]+. A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer the reaction mixture was evaporated to a solid residue This residue was triturated with ethyl acetate (200 mL) filtered Evaporation of the filtrate to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 500-mL Parr hydrogenation vessel was purged with nitrogen and charged with platinum (IV) oxide (1.28 g, 5.64 mmol), 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one oxime (4.00 g, 26.0 mmol), acetic acid (11 mL) and ethanol (110 mL). The bottle was evacuated, charged with hydrogen gas to a pressure of 50 psi and shaken for 24 h on a Parr hydrogenation apparatus. The hydrogen was then evacuated and nitrogen charged to the bottle. The reaction mixture was then mixed with Celite 521 (5.0 g), filtered, and the filtrate evaporated to a solid residue. This residue was dissolved in methanol (100 mL) and this solution treated with sodium carbonate (10 g). The resulting suspension was added diethyl ether (50 mL) and filtered. Evaporation of the filtrate to dryness afforded 3.64 g (100%) of 8-methyl-8-azabicyclo[3.2.1]oct-3-ylamine as a white solid: 1H NMR (300 MHz, CD3OD) δ 5.18 (br s, 2H), 3.35 (br s, 2H), 3.21 (t, J=6.6 Hz, 1H), 2.40 (s, 3H), 2.26-2.00 (m, 6H), 1.68-1.58 (m, 2H). A 500-mL Parr hydrogenation vessel was purged with nitrogen The bottle was evacuated charged with hydrogen gas to a pressure of 50 psi The hydrogen was then evacuated nitrogen charged to the bottle The reaction mixture was then mixed with Celite 521 (5.0 g) filtered the filtrate evaporated to a solid residue This residue was dissolved in methanol (100 mL) this solution treated with sodium carbonate (10 g) The resulting suspension was added diethyl ether (50 mL) filtered Evaporation of the filtrate to dryness

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer was charged with 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one (5.00 g, 35.9 mmol), hydroxylamine hydrochloride (7.08 g, 102 mmol) sodium acetate (39.0 g, 476 mmol) and ethanol (45 mL). After stirring at ambient temperature for 4 h, the reaction mixture was evaporated to a solid residue. This residue was triturated with ethyl acetate (200 mL) and filtered. Evaporation of the filtrate to dryness gave 5.08 g (93% yield) of 8-methyl-8-aza-bicyclo[3.2.1]octan-3-one oxime as a white solid: mp 140-142° C.; 1H NMR (300 MHz, CD3OD) δ 3.76 (m, 2H), 3.33-3.23 (m, 2H), 2.75 (m, 1H), 2.69 (s, 3H), 2.46-2.14 (m, 4H), 1.88-1.66 (m, 2H); MS (APCI) m/z 155 [M+H]+. A 500-mL one-neck round-bottomed flask equipped with a magnetic stirrer the reaction mixture was evaporated to a solid residue This residue was triturated with ethyl acetate (200 mL) filtered Evaporation of the filtrate to dryness