tert-butyl N-[(2R,3R)-2-methylpiperidin-3-yl]carbamate

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

Procedure: tert-Butyl (2R,3R)-2-methylpiperidin-3-ylcarbamate (310) (1.1 g, 5.1 mmol) was dissolved in THF (20 mL). To the stirred solution was added DIEA (1.34 mL, 7.7 mmol), followed by 3,5-dichloropyrazine-2-carbonitrile (1.07 g, 6.2 mmol). The reaction was stirred at room temperature for 1 hour. An additional amount of 3,5-dichloropyrazine-2-carbonitrile (200 mg, 1.2 mmol) was added, and the reaction was stirred for another hour. The solvent was removed under reduced pressure, and the residue was suspended in EtOAc. The organic mixture was washed with 1N HCl (aq), saturated NaHCO3(aq) and brine, dried, and concentrated in vacuo. The residue was then purified by silica flash column chromatography (EtOAc/hexanes) to give tert-butyl (2R,3R)-1-(6-chloro-5-cyanopyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate (311), (1.54 g, 4.38 mmol, 86% yield). the reaction was stirred for another hour The solvent was removed under reduced pressure The organic mixture was washed with 1N HCl (aq), saturated NaHCO3(aq) and brine dried concentrated in vacuo The residue was then purified by silica flash column chromatography (EtOAc/hexanes)

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

Procedure: (2R,3R)-Benzyl 3-(tert-butoxycarbonylamino)-2-methylpiperidine-1-carboxylate (308) (1.7 g, 4.9 mmol) was dissolved in IPA (20 mL). 10% Pd/C (1 g) was added and the mixture was hydrogenated on a Parr shaker at 50 psi pressure for 12 hours. The reaction mixture was filtered through celite, and the solvent was removed under reduced pressure to give tert-butyl (2R,3R)-2-methylpiperidin-3-ylcarbamate (310), (1.1 g, 5.1 mmol, 100% yield). The reaction mixture was filtered through celite the solvent was removed under reduced pressure

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

Procedure: tert-Butyl (2R,3R)-2-methylpiperidin-3-ylcarbamate (310) (1.1 g, 5.1 mmol) was dissolved in THF (20 mL). To the stirred solution was added DIEA (1.34 mL, 7.7 mmol), followed by 3,5-dichloropyrazine-2-carbonitrile (1.07 g, 6.2 mmol). The reaction was stirred at room temperature for 1 hour. An additional amount of 3,5-dichloropyrazine-2-carbonitrile (200 mg, 1.2 mmol) was added, and the reaction was stirred for another hour. The solvent was removed under reduced pressure, and the residue was suspended in EtOAc. The organic mixture was washed with 1N HCl (aq), saturated NaHCO3(aq) and brine, dried, and concentrated in vacuo. The residue was then purified by silica flash column chromatography (EtOAc/hexanes) to give tert-butyl (2R,3R)-1-(6-chloro-5-cyanopyrazin-2-yl)-2-methylpiperidin-3-ylcarbamate (311), (1.54 g, 4.38 mmol, 86% yield). the reaction was stirred for another hour The solvent was removed under reduced pressure The organic mixture was washed with 1N HCl (aq), saturated NaHCO3(aq) and brine dried concentrated in vacuo The residue was then purified by silica flash column chromatography (EtOAc/hexanes)

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

Procedure: (2R,3R)-Benzyl 3-(tert-butoxycarbonylamino)-2-methylpiperidine-1-carboxylate (308) (1.7 g, 4.9 mmol) was dissolved in IPA (20 mL). 10% Pd/C (1 g) was added and the mixture was hydrogenated on a Parr shaker at 50 psi pressure for 12 hours. The reaction mixture was filtered through celite, and the solvent was removed under reduced pressure to give tert-butyl (2R,3R)-2-methylpiperidin-3-ylcarbamate (310), (1.1 g, 5.1 mmol, 100% yield). The reaction mixture was filtered through celite the solvent was removed under reduced pressure