1-benzyl-4-methylpiperidin-3-one

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

Procedure: To a stirred solution of 1-benzyl-4-methyl-piperidin-3-one (2.3 grams, 11.5 mmol), prepared by the methods of lorio, M. A. and Damia, G., Tetrahedron, 26, 5519 (1970) and Grieco et al., Journal of the American Chemical Society, 107, 1768 (1985), (modified using 5% methanol as a co-solvent), both references are incorporated by reference in their entirety, dissolved in 23 mL of 2 M methylamine in tetrahydrofuran was added 1.4 mL (23 mmol) of acetic acid and the resulting mixture stirred in a sealed tube for 16 hours at room temperature. Triacetoxy sodium borohydride (4.9 grams, 23 mmol) was added and the new mixture stirred at room temperature in a sealed tube for 24 h, at which time, the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL). The reaction mixture was then extracted 3×80 mL with ether, the combined ether layers dried over sodium sulfate (Na2SO4) and concentrated to dryness in vacuo affording 1.7 grams (69%) of the title compound as a white solid. LRMS: 219.1 (M+1). the new mixture stirred at room temperature in a sealed tube for 24 h, at which time the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL) The reaction mixture was then extracted 3×80 mL with ether the combined ether layers dried over sodium sulfate (Na2SO4) concentrated to dryness in vacuo

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

Procedure: To a stirred solution of 1-benzyl-4-methyl-piperidin-3-one (2.3 grams, 11.5 mmol), prepared by the methods of lorio, M. A. and Damia, G., Tetrahedron, 26, 5519 (1970) and Grieco et al., Journal of the American Chemical Society, 107, 1768 (1985), (modified using 5% methanol as a co-solvent), both references are incorporated by reference in their entirety, dissolved in 23 mL of 2 M methylamine in tetrahydrofuran was added 1.4 mL (23 mmol) of acetic acid and the resulting mixture stirred in a sealed tube for 16 hours at room temperature. Triacetoxy sodium borohydride (4.9 grams, 23 mmol) was added and the new mixture stirred at room temperature in a sealed tube for 24 h, at which time, the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL). The reaction mixture was then extracted 3×80 mL with ether, the combined ether layers dried over sodium sulfate (Na2SO4) and concentrated to dryness in vacuo affording 1.7 grams (69%) of the title compound as a white solid. LRMS: 219.1 (M+1). the new mixture stirred at room temperature in a sealed tube for 24 h, at which time the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL) The reaction mixture was then extracted 3×80 mL with ether the combined ether layers dried over sodium sulfate (Na2SO4) concentrated to dryness in vacuo

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

Procedure: To a stirred solution of 1-benzyl-4-methyl-piperidin-3-one (2.3 grams, 11.5 mmol), prepared by the methods of lorio, M. A. and Damia, G., Tetrahedron, 26, 5519 (1970) and Grieco et al., Journal of the American Chemical Society, 107, 1768 (1985), (modified using 5% methanol as a co-solvent), both references are incorporated by reference in their entirety, dissolved in 23 mL of 2 M methylamine in tetrahydrofuran was added 1.4 mL (23 mmol) of acetic acid and the resulting mixture stirred in a sealed tube for 16 hours at room temperature. Triacetoxy sodium borohydride (4.9 grams, 23 mmol) was added and the new mixture stirred at room temperature in a sealed tube for 24 h, at which time, the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL). The reaction mixture was then extracted 3×80 mL with ether, the combined ether layers dried over sodium sulfate (Na2SO4) and concentrated to dryness in vacuo affording 1.7 grams (69%) of the title compound as a white solid. LRMS: 219.1 (M+1). the new mixture stirred at room temperature in a sealed tube for 24 h, at which time the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL) The reaction mixture was then extracted 3×80 mL with ether the combined ether layers dried over sodium sulfate (Na2SO4) concentrated to dryness in vacuo

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

Procedure: To a stirred solution of 1-benzyl-4-methyl-piperidin-3-one (2.3 grams, 11.5 mmol), prepared by the methods of Iorio, M. A. and Damia, G., Tetrahedron, 26, 5519 (1970) and Grieco et al., Journal of the American Chemical Society, 107, 1768 (1985), (modified using 5% methanol as a co-solvent), both references are incorporated by reference in their entirety, dissolved in 23 mL of 2 M methylamine in tetrahydrofuran was added 1.4 mL (23 mmol) of acetic acid and the resulting mixture stirred in a sealed tube for 16 hours at room temperature. Triacetoxy sodium borohydride (4.9 grams, 23 mmol) was added and the new mixture stirred at room temperature in a sealed tube for 24 h, at which time, the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL). The reaction mixture was then extracted 3×80 mL with ether, the combined ether layers dried over sodium sulfate (Na2SO4) and concentrated to dryness in vacuo affording 1.7 grams (69%) of the title compound as a white solid. LRMS: 219.1 (M+1). the new mixture stirred at room temperature in a sealed tube for 24 h, at which time the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL) The reaction mixture was then extracted 3×80 mL with ether the combined ether layers dried over sodium sulfate (Na2SO4) concentrated to dryness in vacuo

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

Procedure: To a stirred solution of 1-benzyl-4-methyl-piperidin-3-one (2.3 grams, 11.5 mmol), prepared by the methods of Iorio, M. A. and Damia, G., Tetrahedron, 26, 5519 (1970) and Grieco et al., Journal of the American Chemical Society, 107, 1768 (1985), (modified using 5% methanol as a co-solvent), both references are incorporated by reference in their entirety, dissolved in 23 mL of 2 M methylamine in tetrahydrofuran was added 1.4 mL (23 mmol) of acetic acid and the resulting mixture stirred in a sealed tube for 16 hours at room temperature. Triacetoxy sodium borohydride (4.9 grams, 23 mmol) was added and the new mixture stirred at room temperature in a sealed tube for 24 h, at which time, the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL). The reaction mixture was then extracted 3×80 mL with ether, the combined ether layers dried over sodium sulfate (Na2SO4) and concentrated to dryness in vacuo affording 1.7 grams (69%) of the title compound as a white solid. LRMS: 219.1 (M+1). the new mixture stirred at room temperature in a sealed tube for 24 h, at which time the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL) The reaction mixture was then extracted 3×80 mL with ether the combined ether layers dried over sodium sulfate (Na2SO4) concentrated to dryness in vacuo

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

Procedure: To a stirred solution of 1-benzyl-4-methyl-piperidin-3-one (2.3 grams, 11.5 mmol), prepared by the methods of Iorio, M. A. and Damia, G., Tetrahedron, 26, 5519 (1970) and Grieco et al., Journal of the American Chemical Society, 107, 1768 (1985), (modified using 5% methanol as a co-solvent), both references are incorporated by reference in their entirety, dissolved in 23 mL of 2 M methylamine in tetrahydrofuran was added 1.4 mL (23 mmol) of acetic acid and the resulting mixture stirred in a sealed tube for 16 hours at room temperature. Triacetoxy sodium borohydride (4.9 grams, 23 mmol) was added and the new mixture stirred at room temperature in a sealed tube for 24 h, at which time, the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL). The reaction mixture was then extracted 3×80 mL with ether, the combined ether layers dried over sodium sulfate (Na2SO4) and concentrated to dryness in vacuo affording 1.7 grams (69%) of the title compound as a white solid. LRMS: 219.1 (M+1). the new mixture stirred at room temperature in a sealed tube for 24 h, at which time the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL) The reaction mixture was then extracted 3×80 mL with ether the combined ether layers dried over sodium sulfate (Na2SO4) concentrated to dryness in vacuo

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

Procedure: To a stirred solution of 1-benzyl-4-methyl-piperidin-3-one (2.3 grams, 11.5 mmol), prepared by the methods of Iorio, M. A. and Damia, G., Tetrahedron, 26, 5519 (1970) and Grieco et al., Journal of the American Chemical Society, 107, 1768 (1985), (modified using 5% methanol as a co-solvent), both references are incorporated by reference in their entirety, dissolved in 23 mL of 2 M methylamine in tetrahydrofuran was added 1.4 mL (23 mmol) of acetic acid and the resulting mixture stirred in a sealed tube for 16 hours at room temperature. Triacetoxy sodium borohydride (4.9 grams, 23 mmol) was added and the new mixture stirred at room temperature in a sealed tube for 24 h, at which time, the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL). The reaction mixture was then extracted 3×80 mL with ether, the combined ether layers dried over sodium sulfate (Na2SO4) and concentrated to dryness in vacuo affording 1.7 grams (69%) of the title compound as a white solid. LRMS: 219.1 (M+1). the new mixture stirred at room temperature in a sealed tube for 24 h, at which time the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL) The reaction mixture was then extracted 3×80 mL with ether the combined ether layers dried over sodium sulfate (Na2SO4) concentrated to dryness in vacuo

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

Procedure: To a stirred solution of the product from Method E (3.81 grams/0.019 mol) and 38 mL of 2.0 M methylamine in THF was added 2.2 mL of acetic acid and the resulting mixture stirred at room temperature for 1.5 hours. Triacetoxysodiumborohydride (NaB(OAc)3H) (7.94 grams/0.038 mol) was added as a solid and the new mixture stirred at room temperature for 18 hours. The reaction was quenched with 2 N hydrochloric acid and the pH adjusted to 1. The reaction mixture was washed two times with ether, the aqueous layer then adjusted to pH of 12 with 6 N sodium hydroxide (aq) and extracted three times with dichloromethane The combined dichloromethane layers were dried over Na2SO4, filtered and evaporated to dryness in vacuo affording 3.51 grams (87.75%) of the title compound as dark yellow oil. LRMS: 219.1 (M+1). the new mixture stirred at room temperature for 18 hours The reaction was quenched with 2 N hydrochloric acid The reaction mixture was washed two times with ether extracted three times with dichloromethane The combined dichloromethane layers were dried over Na2SO4 filtered evaporated to dryness in vacuo

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

Procedure: To a solution of the product from Method D (9.8 grams/0.026 mol) and 31.7 mL of diisopropylethylamine dissolved in 250 mL of dichloromethane and cooled to 0° C. was added (dropwise) 12.4 grams of SO3 pyridine complex dissolved in 153 mL of dimethylsulfoxide over a 40 minute period. Once added, the reaction stirred for 1.5 hours at room temperature and was then quenched upon addition of 200 mL of saturated NaHCO3 (aq). The dichloromethane was removed in vacuo and the remaining aqueous residue extracted four times with diisopropyl ether (150 mL). The combined ether layers were washed four times with water (100 mL), dried over Na2SO4 and concentrated to dryness in vacuo affording 3.81 grams (72.97%) of the title compound as yellow oil. LRMS: 204 (M+1). was added (dropwise) 12.4 grams of SO3 pyridine complex Once added was then quenched upon addition of 200 mL of saturated NaHCO3 (aq) The dichloromethane was removed in vacuo the remaining aqueous residue extracted four times with diisopropyl ether (150 mL) The combined ether layers were washed four times with water (100 mL) dried over Na2SO4 concentrated to dryness in vacuo

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

Procedure: To a stirred solution of 1-benzyl-4-methyl-piperidin-3-one (2.3 grams, 11.5 mmol), prepared by the methods of lorio, M. A. and Damia, G., Tetrahedron, 26, 5519 (1970) and Grieco et al., Journal of the American Chemical Society, 107, 1768 (1985), (modified using 5% methanol as a co-solvent), both references are incorporated by reference in their entirety, dissolved in 23 mL of 2 M methylamine in tetrahydrofuran was added 1.4 mL (23 mmol) of acetic acid and the resulting mixture stirred in a sealed tube for 16 hours at room temperature. Triacetoxy sodium borohydride (4.9 grams, 23 mmol) was added and the new mixture stirred at room temperature in a sealed tube for 24 h, at which time, the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL). The reaction mixture was then extracted 3 ×80 mL with ether, the combined ether layers dried over sodium sulfate (Na2SO4) and concentrated to dryness in vacuo affording 1.7 grams (69%) of the title compound as a white solid. LRMS: 219.1 (M+1). the new mixture stirred at room temperature in a sealed tube for 24 h, at which time the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL) The reaction mixture was then extracted 3 ×80 mL with ether the combined ether layers dried over sodium sulfate (Na2SO4) concentrated to dryness in vacuo

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

Procedure: To a stirred solution of 1-benzyl-4-methyl-piperidin-3-one (2.3 grams, 11.5 mmol), prepared by the methods of Iorio, M. A. and Damia, G., Tetrahedron, 26, 5519 (1970) and Grieco et al., Journal of the American Chemical Society, 107, 1768 (1985), (modified using 5% methanol as a co-solvent), both references are incorporated by reference in their entirety, dissolved in 23 mL of 2 M methylamine in tetrahydrofuran was added 1.4 mL (23 mmol) of acetic acid and the resulting mixture stirred in a sealed tube for 16 hours at room temperature. Triacetoxy sodium borohydride (4.9 grams, 23 mmol) was added and the new mixture stirred at room temperature in a sealed tube for 24 h, at which time, the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL). The reaction mixture was then extracted 3×80 mL with ether, the combined ether layers dried over sodium sulfate (Na2SO4) and concentrated to dryness in vacuo affording 1.7 grams (69%) of the title compound as a white solid. LRMS: 219.1 (M+1). the new mixture stirred at room temperature in a sealed tube for 24 h, at which time the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL) The reaction mixture was then extracted 3×80 mL with ether the combined ether layers dried over sodium sulfate (Na2SO4) concentrated to dryness in vacuo

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

Procedure: To a stirred solution of 1-benzyl-4-methyl-piperidin-3-one (2.3 grams, 11.5 mmol), prepared by the methods of Iorio, M. A. and Damia, G., Tetrahedron, 26, 5519 (1970) and Grieco et al., Journal of the American Chemical Society, 107, 1768 (1985), (modified using 5% methanol as a co-solvent), both references are incorporated by reference in their entirety, dissolved in 23 mL of 2 M methylamine in tetrahydrofuran was added 1.4 mL (23 mmol) of acetic acid and the resulting mixture stirred in a sealed tube for 16 hours at room temperature. Triacetoxy sodium borohydride (4.9 grams, 23 mmol) was added and the new mixture stirred at room temperature in a sealed tube for 24 h, at which time, the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL). The reaction mixture was then extracted 3×80 mL with ether, the combined ether layers dried over sodium sulfate (Na2SO4) and concentrated to dryness in vacuo affording 1.7 grams (69%) of the title compound as a white solid. LRMS: 219.1 (M+1). the new mixture stirred at room temperature in a sealed tube for 24 h, at which time the reaction was quenched upon addition of 1 N sodium hydroxide (50 mL) The reaction mixture was then extracted 3×80 mL with ether the combined ether layers dried over sodium sulfate (Na2SO4) concentrated to dryness in vacuo