tert-butyl 4-(piperidin-4-ylmethyl)piperidine-1-carboxylate

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

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

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

Procedure: 1,1-Dimethylethyl 4-(4-piperidinylmethyl)-1-piperidinecarboxylate (may be prepared as described in Description 2) (1.5 g), and LiAlH4 (26.6 ml of 1M solution in tetrahydrofuran) were combined in tetrahydrofuran (10 ml) and the reaction mixture stirred at room temperature for 10 min before cooling to 0° C. in an ice/water bath. Ethyl formate (5 ml) was then added dropwise. The reaction was then quenched with 3 N sodium hydroxide solution. The solid precipitate formed was filtered and washed with more tetrahydrofuran. The combined organics were dried over Na2SO4, and evaporated to give the title compound (D18) (1.1 g). before cooling to 0° C. in an ice/water bath The reaction was then quenched with 3 N sodium hydroxide solution The solid precipitate formed was filtered washed with more tetrahydrofuran The combined organics were dried over Na2SO4 evaporated

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

Procedure: 1,1-Dimethylethyl 4-(4-piperidinylmethyl)-1-piperidinecarboxylate (may be prepared as described in Description 2) (2.0 g), cyclopropyl carboxaldehyde (1.6 ml) and triethylamine (1.99 ml) were stirred in dichloromethane (70 ml) at room temperature. After 10 min sodium triacetoxyborohydride (3.1 g) was added and the reaction was stirred at room temperature overnight. The reaction mixture was washed with saturated potassium carbonate solution (2×50 ml), saturated sodium hydrogen carbonate solution (2×50 ml) and saturated brine (50 ml). The organic phase was dried (MgSO4) and evaporated to give the title compound (D9) (2.0 g). The reaction mixture was washed with saturated potassium carbonate solution (2×50 ml), saturated sodium hydrogen carbonate solution (2×50 ml) and saturated brine (50 ml) The organic phase was dried (MgSO4) evaporated

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

Procedure: 1,1-Dimethylethyl 4-(4-piperidinylmethyl)-1-piperidinecarboxylate (may be prepared as described in Description 2) (2 g), ethyl iodide (0.57 ml) and K2CO3 (1.96 g) were combined in acetonitrile (70 ml) and the reaction mixture was stirred at room temperature for 3 h. The reaction was filtered to remove solids and the solvent evaporated to give the title compound (D7) as a yellow solid (2.5 g). The reaction was filtered to remove solids the solvent evaporated

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

Procedure: 1,1-Dimethylethyl 4-(4-piperidinylmethyl)-1-piperidinecarboxylate (may be prepared as described in Description 2) (4.8 g), cyclobutanone (3.81 ml) and triethylamine (4.7 ml) were stirred in DCM (200 ml) at room temperature. After 10 min sodium triacetoxyborohydride (7.2 g) was added and the reaction was stirred at room temperature overnight. The reaction mixture was evaporated and redissolved in dichloromethane (50 ml). After washing with saturated potassium carbonate solution (2×50 ml), saturated sodium hydrogen carbonate solution (2×50 ml) and saturated brine (50 ml) the organic phase was dried (MgSO4) and evaporated to give the title compound (D5) as a colourless solid (5.72 g). The reaction mixture was evaporated redissolved in dichloromethane (50 ml) After washing with saturated potassium carbonate solution (2×50 ml), saturated sodium hydrogen carbonate solution (2×50 ml) and saturated brine (50 ml) the organic phase was dried (MgSO4) evaporated

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,1-Dimethylethyl 4-(4-piperidinylmethyl)-1-piperidinecarboxylate (may be prepared as described in Description 2) (3 g), isopropyl iodide (3.2 ml) and K2CO3 (2.94 g) were combined in acetonitrile (70 ml) and the reaction mixture heated at 50° C. overnight. The reaction was allowed to cool to room temperature, filtered and evaporated. The residue was dissolved in diethylether (50 ml) and washed successively with water (50 ml), saturated sodium thiosulphate solution (50 ml), saturated brine (50 ml) and dried (Na2SO4). The solvent was evaporated to give the title compound (D3) as a pale yellow oil (3.1 g). to cool to room temperature filtered evaporated The residue was dissolved in diethylether (50 ml) washed successively with water (50 ml), saturated sodium thiosulphate solution (50 ml), saturated brine (50 ml) dried (Na2SO4) The solvent was evaporated

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

Procedure: 1,1-Dimethylethyl 4-(4-pyridinylmethyl)-1-piperidinecarboxylate (may be prepared as described in Description 1) (11.4 g) was dissolved in ethanol (200 ml) and acetic acid (2.36 ml). Platinum oxide (2 g) was added under a blanket of argon, and the reaction shaken under hydrogen at 50 psi for 18 h. After carefully filtering off the platinum catalyst, the solvent was evaporated and the residue redissolved in ethyl acetate (50 ml) and washed with saturated sodium hydrogen carbonate solution (50 ml). The aqueous phase was extracted into ethyl acetate (2×50 ml) and the combined organics dried (Na2SO4) and evaporated to give the title compound (D2) as white solid (9.4 g). After carefully filtering off the platinum catalyst the solvent was evaporated the residue redissolved in ethyl acetate (50 ml) washed with saturated sodium hydrogen carbonate solution (50 ml) The aqueous phase was extracted into ethyl acetate (2×50 ml) the combined organics dried (Na2SO4) evaporated