ditert-butyl (2S)-6-oxopiperidine-1,2-dicarboxylate

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

Procedure: To a solution of (S)-6-oxo-piperidine-1,2-dicarboxylic acid di-tert-butyl ester (6.30 g, 21.0 mmol) in ethyl acetate (50 mL) was added 1.1-M HCl in ethyl acetate (28.7 mL, 31.5 mmol). The reaction was stirred at room temperature for 1 h, then washed with water, saturated aq.NaHCO3 and brine. The organic phase was dried (MgSO4), filtered and evaporated to afford the title compound as a yellow oil which crystallized upon standing (3.11 g, 74%): 1H NMR (400 MHz, CDCl3) δ 1.49 (9H, s), 1.74-1.94 (3H, m), 2.18 (1H, m), 2.29-2.44 (2H, m), 3.95-3.98 (1H, m), 6.32 (1H, br s); 13C NMR (100 MHz, CDCl3) δ 19.9 (CH2), 25.9 (CH2), 28.4 (CH3), 31.4 (CH2), 55.7 (CH), 83.0 (C), 170.4 (C), 171.9 (C). washed with water The organic phase was dried (MgSO4) filtered evaporated

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

Procedure: To a solution of (S)-6-oxo-piperidine-1,2-dicarboxylic acid di-tert-butyl ester (6.30 g, 21.0 mmol) in ethyl acetate (50 mL) was added 1.1-M HCl in ethyl acetate (28.7 mL, 31.5 mmol). The reaction was stirred at room temperature for 1 h, then washed with water, saturated aq.NaHCO3 and brine. The organic phase was dried (MgSO4), filtered and evaporated to afford the title compound as a yellow oil which crystallized upon standing (3.11 g, 74%): 1H NMR (400 MHz, CDCl3) δ 1.49 (9H, s), 1.74-1.94 (3H, m), 2.18 (1H, m), 2.29-2.44 (2H, m), 3.95-3.98 (1H, m), 6.32 (1H, br s); 13C NMR (100 MHz, CDCl3) δ 19.9 (CH2), 25.9 (CH2), 28.4 (CH3), 31.4 (CH2), 55.7 (CH), 83.0 (C), 170.4 (C), 171.9 (C). washed with water The organic phase was dried (MgSO4) filtered evaporated

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

Procedure: To a vigorously stirred solution of RuCl3.H2O (2.39 g, 11.5 mmol) and NaIO4 (24.6 g, 115.0 mmol) in water (250 mL) was added (S)-piperidine-1,2-dicarboxylic acid di-tert-butyl ester (8.22 g, 28.8 mmol) in ethyl acetate (250 mL) at room temperature. After stirring for 4 h, the reaction mixture was partitioned and the aqueous layer washed with ethyl acetate. To the combined organic layers was added iPrOH (2.5 mL) and stirring was continued for 2 hours in order to destroy excess RuO4. The precipitate was removed by filtration through a pad of celite and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography (30% ethyl acetate in hexane) to afford the title compound as a pale yellow oil, which crystallized upon standing (6.69 g, 78%): 1H NMR (400 MHz, CDCl3) δ 1.49 (9H, s), 1.52 (9H, s), 1.75-1.82 (2H, m), 1.97-2.06 (1H, m), 2.15-2.21 (1H, m), 2.41-2.61 (2H, m), 4.59 (1H, dd, J 3.5 Hz) Method I: the reaction mixture was partitioned the aqueous layer washed with ethyl acetate To the combined organic layers was added iPrOH (2.5 mL) stirring was continued for 2 hours in order to destroy excess RuO4 The precipitate was removed by filtration through a pad of celite the filtrate was evaporated under reduced pressure The residue was purified by flash chromatography (30% ethyl acetate in hexane)

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

Procedure: To a solution of (S)-6-oxo-piperidine-1,2-dicarboxylic acid di-tert-butyl ester (6.30 g, 21.0 mmol) in ethyl acetate (50 mL) was added 1.1-M HCl in ethyl acetate (28.7 mL, 31.5 mmol). The reaction was stirred at room temperature for 1 h, then washed with water, saturated aq.NaHCO3 and brine. The organic phase was dried (MgSO4), filtered and evaporated to afford the title compound as a yellow oil which crystallized upon standing (3.11 g, 74%): 1H NMR (400 MHz, CDCl3) δ 1.49 (9H, s), 1.74-1.94 (3H, m), 2.18 (1H, m), 2.29-2.44 (2H, m), 3.95-3.98 (1H, m), 6.32 (1H, br s); 13C NMR (100 MHz, CDCl3) δ 19.9 (CH2), 25.9 (CH2), 28.4 (CH3), 31.4 (CH2), 55.7 (CH), 83.0 (C), 170.4 (C), 171.9 (C). washed with water The organic phase was dried (MgSO4) filtered evaporated

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

Procedure: To a vigorously stirred solution of RuCl3.H2O (2.39 g, 11.5 mmol) and NaIO4 (24.6 g, 115.0 mmol) in water (250 mL) was added (S)-piperidine-1,2-dicarboxylic acid di-tert-butyl ester (8.22 g, 28.8 mmol) in ethyl acetate (250 mL) at room temperature. After stirring for 4 h, the reaction mixture was partitioned and the aqueous layer washed with ethyl acetate. To the combined organic layers was added iPrOH (2.5 mL) and stirring was continued for 2 hours in order to destroy excess RuO4. The precipitate was removed by filtration through a pad of celite and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography (30% ethyl acetate in hexane) to afford the title compound as a pale yellow oil, which crystallized upon standing (6.69 g, 78%): 1H NMR (400 MHz, CDCl3) δ 1.49 (9H, s), 1.52 (9H, s), 1.75-1.82 (2H, m), 1.97-2.06 (1H, m), 2.15-2.21 (1H, m), 2.41-2.61 (2H, m), 4.59 (1H, dd, J 3.5 Hz) the reaction mixture was partitioned the aqueous layer washed with ethyl acetate To the combined organic layers was added iPrOH (2.5 mL) stirring was continued for 2 hours in order to destroy excess RuO4 The precipitate was removed by filtration through a pad of celite the filtrate was evaporated under reduced pressure The residue was purified by flash chromatography (30% ethyl acetate in hexane)

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

Procedure: To a solution of (S)-6-oxo-piperidine-1,2-dicarboxylic acid di-tert-butyl ester (6.30 g, 21.0 mmol) in ethyl acetate (50 mL) was added 1.1-M HCl in ethyl acetate (28.7 mL, 31.5 mmol). The reaction was stirred at room temperature for 1 h, then washed with water, saturated aq.NaHCO3 and brine. The organic phase was dried (MgSO4), filtered and evaporated to afford the title compound as a yellow oil which crystallized upon standing (3.11 g, 74%): 1H NMR (400 MHz, CDCl3) δ 1.49 (9H, s), 1.74-1.94 (3H, m), 2.18 (1H, m), 2.29-2.44 (2H, m), 3.95-3.98 (1H, m), 6.32 (1H, br s); 13C NMR (100 MHz, CDCl3) δ 19.9 (CH2), 25.9 (CH2), 28.4 (CH3), 31.4 (CH2), 55.7 (CH), 83.0 (C), 170.4 (C), 171.9 (C). washed with water The organic phase was dried (MgSO4) filtered evaporated

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

Procedure: To a vigorously stirred solution of RuCl3.H2O (2.39 g, 11.5 mmol) and NaIO4 (24.6 g, 115.0 mmol) in water (250 mL) was added (S)-piperidine-1,2-dicarboxylic acid di-tert-butyl ester (8.22 g, 28.8 mmol) in ethyl acetate (250 mL) at room temperature. After stirring for 4 h, the reaction mixture was partitioned and the aqueous layer washed with ethyl acetate. To the combined organic layers was added iPrOH (2.5 mL) and stirring was continued for 2 hours in order to destroy excess RuO4. The precipitate was removed by filtration through a pad of celite and the filtrate was evaporated under reduced pressure. The residue was purified by flash chromatography (30% ethyl acetate in hexane) to afford the title compound as a pale yellow oil, which crystallized upon standing (6.69 g, 78%): 1H NMR (400 MHz, CDCl3) δ 1.49 (9H, s), 1.52 (9H, s), 1.75-1.82 (2H, m), 1.97-2.06 (1H, m), 2.15-2.21 (1H, m), 2.41-2.61 (2H, m), 4.59 (1H, dd, J=3.5 Hz) the reaction mixture was partitioned the aqueous layer washed with ethyl acetate To the combined organic layers was added iPrOH (2.5 mL) stirring was continued for 2 hours in order to destroy excess RuO4 The precipitate was removed by filtration through a pad of celite the filtrate was evaporated under reduced pressure The residue was purified by flash chromatography (30% ethyl acetate in hexane)