2-(4-oxopiperidin-1-yl)benzonitrile

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of 5 (200 mg, 1.00 mmol), 1 (161 mg, 1.00 mmol), and acetic acid (300 mg, 5.00 mmol) in methanol (2 mL) was treated with sodium cyanoborohydride (66 mg, 1.05 mmol) at room temperature. The resulting mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the residue dissolved in dichloromethane and sodium bicarbonate solution. The aqueous layer was extracted with three additional portions of dichloromethane and the combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. PCTLC (SiO2, 4 mm, 10% EtOH-90% CHCl3) afforded the title compound (12). The solvent was removed in vacuo the residue dissolved in dichloromethane The aqueous layer was extracted with three additional portions of dichloromethane the combined organic extracts were washed with brine dried over Na2SO4 concentrated under reduced pressure

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

Procedure: A solution of 5 (200 mg, 1.00 mmol), 1 (161 mg, 1.00 mmol), and acetic acid (300 mg, 5.00 mmol) in methanol (2 mL) was treated with sodium cyanoborohydride (66 mg, 1.05 mmol) at room temperature. The resulting mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the residue dissolved in dichloromethane and sodium bicarbonate solution. The aqueous layer was extracted with three additional portions of dichloromethane and the combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. PCTLC (SiO2, 4 mm, 10% EtOH-90% CHCl3) afforded the title compound (12). The solvent was removed in vacuo the residue dissolved in dichloromethane The aqueous layer was extracted with three additional portions of dichloromethane the combined organic extracts were washed with brine dried over Na2SO4 concentrated under reduced pressure

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

Procedure: A solution of 4 (533 mg, 2.18 mmol) in ether (10 mL) was treated with 5% aqueous HCl (20 mL). The mixture was stirred at room temperature (11 d). The reaction was diluted with ether and neutralized with sodium bicarbonate solution. The aqueous layer was extracted with two additional portions of ether and the combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. PCTLC (SiO2, 4 mm, 20% EtOAc-80% hexane) afforded the title compound (5). The aqueous layer was extracted with two additional portions of ether the combined organic extracts were washed with brine dried over Na2SO4 concentrated under reduced pressure

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

Procedure: The title compound was prepared from 21 (1.13 g, 5.6 mmol) and 5 (750 mg, 3.75 mmol) using the procedure described in 16 to give the title compound.

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

Procedure: To a solution of 2-(4-oxo-piperidin-1-yl)-benzonitrile (5) (653 mg, 3.26 mmol) and 4 (890 mg, 3.58 mmol) in 40 ml of methanol was added 4 g of powdered 4 Å molecular sieves. The resulting suspension was stirred at room temperature for 24 hours. The suspension was subsequently acidified to pH 5 with acetic acid and a 1M solution of NaCNBH3 in THF (6.0 ml 5.6 mmol) was added slowly with a syringe pump over 24 hours. When the addition was complete, the solvent was removed in vacuo and the residue taken up in chloroform and filtered. The solution was then washed with 10% Na2CO3, dried over MgSO4, and the solvent removed in vacuo to give the crude amine. The crude product was purified by chromatography on silica gel (5% MeOH/CHCl3) to give the title compound. When the addition the solvent was removed in vacuo filtered The solution was then washed with 10% Na2CO3 dried over MgSO4 the solvent removed in vacuo to give the crude amine The crude product was purified by chromatography on silica gel (5% MeOH/CHCl3)

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

Procedure: A solution of 5 (200 mg, 1.00 mmol), 1 (161 mg, 1.00 mmol), and acetic acid (300 mg, 5.00 mmol) in methanol (2 mL) was treated with sodium cyanoborohydride (66 mg, 1.05 mmol) at room temperature. The resulting mixture was stirred at room temperature overnight. The solvent was removed in vacuo and the residue dissolved in dichloromethane and sodium bicarbonate solution. The aqueous layer was extracted with three additional portions of dichloromethane and the combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. PCTLC (SiO2, 4 mm, 10% EtOH-90% CHCl3) afforded the title compound (12). The solvent was removed in vacuo the residue dissolved in dichloromethane The aqueous layer was extracted with three additional portions of dichloromethane the combined organic extracts were washed with brine dried over Na2SO4 concentrated under reduced pressure

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

Procedure: A solution of 4 (533 mg, 2.18 mmol) in ether (10 mL) was treated with 5% aqueous HCl (20 mL). The mixture was stirred at room temperature (11 d). The reaction was diluted with ether and neutralized with sodium bicarbonate solution. The aqueous layer was extracted with two additional portions of ether and the combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. PCTLC (SiO2, 4 mm, 20% EtOAc-80% hexane) afforded the title compound (5). The aqueous layer was extracted with two additional portions of ether the combined organic extracts were washed with brine dried over Na2SO4 concentrated under reduced pressure