tert-butyl 4-(cyanomethyl)piperidine-1-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add trifluoroacetic acid (23 mL, 34.7 g, 304 mmol) to 4-cyanomethylpiperidine-1-carboxylic acid t-butyl ester (5.43 g, 24.21 mmol) in DCM (25 mL) and stir at room temperature for 18 hr. Remove the solvent in vacuo and dissolve in methanol (50 mL) and pour onto an SCX-2 column. Elute with 2 M ammonia in methanol and evaporate the eluent to give piperidin-4-ylacetonitrile as an oil which solidifies on standing (2.78 g, 92%). MS (m/z): 125.1 (M+1). Remove the solvent in vacuo dissolve in methanol (50 mL) pour onto an SCX-2 column Elute with 2 M ammonia in methanol evaporate the eluent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 4-cyanomethylenepiperidine-1-carboxylic acid t-butyl ester (5.39 g, 24.25 mmol) in ethanol (160 mL) to a suspension of 5% palladium on charcoal (0.69 g) in ethanol (20 mL) and hydrogenate at room temperature with agitation at 60 psi for 6 hr. Filter the mixture through celite and evaporate the solvent in vacuo to give 4-cyanomethylpiperidine-1-carboxylic acid t-butyl ester as an oil which solidifies on standing to give a solid (5.43 g, 99.8%). MS (m/z): 247 (M+Na). Filter the mixture through celite evaporate the solvent in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Add 4-cyanomethylenepiperidine-1-carboxylic acid t-butyl ester (5.39 g, 24.25 mmol) in ethanol (160 mL) to a suspension of 5% palladium on charcoal (0.69 g) in ethanol (20 mL) and hydrogenate at room temperature with agitation at 60 psi for 6 hr. Filter the mixture through celite and evaporate the solvent in vacuo to give 4-cyanomethylpiperidine-1-carboxylic acid t-butyl ester as an oil which solidifies on standing to give a solid (5.43 g, 99.8%). MS (m/z): 247 (M+Na). Filter the mixture through celite evaporate the solvent in vacuo

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Cyanomethylene-piperidine-1-carboxylic acid tert-butyl ester (compound of Example 14; 6.9 g, 31.0 mmol) and Pd/C (0.7 g) in ethanol (150 mL) was maintained under hydrogen atmosphere for 8 h. The reaction mixture was filtered through Celite and the solvent was evaporated to afford the title compound. The reaction mixture was filtered through Celite the solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4-Cyanomethylene-piperidine-1-carboxylic acid tert-butyl ester (compound of Example 14; 6.9 g, 31.0 mmol) and Pd/C (0.7 g) in ethanol (150 mL) was maintained under hydrogen atmosphere for 8 h. The reaction mixture was filtered through Celite and the solvent was evaporated to afford the title compound. The reaction mixture was filtered through Celite the solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-(hydroxymethyl)piperidine-1-carboxylic acid tert-butyl ester (9.0 g, 42 mmol) in acetonitril (125 mL) was added triethylamine (5.5 g, 54 mmol) followed by dropwise addition of methanesulfonyl chloride (5.7 g, 50 mmol). When addition was complete the mixture was stirred overnight. The mixture was filtered and the solvent was evaporated. The residue was dissolved in ethyl acetate (100 mL) and the organic solution was washed with water (2×10 mL) and brine. The organic phase was dried (MgSO4) and the solvent was evaporated to give a residue that was dissolved in absolute ethanol (250 mL). Potassium cyanide (8.2 g, 125 mmol) was added and the mixture was heated at reflux overnight. The reaction mixture was allowed to cool to ambient temperature, filtered and the solvent was evaporated. The residue was dissolved in diethyl ether (200 mL) and the organic solution was washed with water (2×20 mL) and then dried (MgSO4) in the presence of activated carbon. The mixture was filtered and the solvent was evaporated to give 9.2 g of 4-(cyanomethyl)piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (400 MHz, CDCl3) δ 1.20-1.33 (m, 2H), 1.46 (s, 9H), 1.77-1.88 (m, 3H), 2.32 (d, 2H), 2.66-2.78 (m, 2H), 4.10-4.23 (m, 2H). When addition The mixture was filtered the solvent was evaporated The residue was dissolved in ethyl acetate (100 mL) the organic solution was washed with water (2×10 mL) and brine The organic phase was dried (MgSO4) the solvent was evaporated to give a residue that the mixture was heated at reflux overnight filtered the solvent was evaporated The residue was dissolved in diethyl ether (200 mL) the organic solution was washed with water (2×20 mL) dried (MgSO4) in the presence of activated carbon The mixture was filtered the solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 4-(hydroxymethyl)piperidine-1-carboxylic acid tert-butyl ester (9.0 g, 42 mmol) in acetonitril (125 mL) was added triethylamine (5.5 g, 54 mmol) followed by dropwise addition of methanesulfonyl chloride (5.7 g, 50 mmol). When addition was complete the mixture was stirred overnight. The mixture was filtered and the solvent was evaporated. The residue was dissolved in ethyl acetate (100 mL) and the organic solution was washed with water (2×10 mL) and brine. The organic phase was dried (MgSO4) and the solvent was evaporated to give a residue that was dissolved in absolute ethanol (250 mL). Potassium cyanide (8.2 g, 125 mmol) was added and the mixture was heated at reflux overnight. The reaction mixture was allowed to cool to ambient temperature, filtered and the solvent was evaporated. The residue was dissolved in diethyl ether (200 mL) and the organic solution was washed with water (2×20 mL) and then dried (MgSO4) in the presence of activated carbon. The mixture was filtered and the solvent was evaporated to give 9.2 g of 4-(cyanomethyl)piperidine-1-carboxylic acid tert-butyl ester. 1H NMR (400 MHz, CDCl3) δ 1.20-1.33 (m, 2H), 1.46 (s, 9H), 1.77-1.88 (m, 3H), 2.32 (d, 2H), 2.66-2.78 (m, 2H), 4.10-4.23 (m, 2H). When addition The mixture was filtered the solvent was evaporated The residue was dissolved in ethyl acetate (100 mL) the organic solution was washed with water (2×10 mL) and brine The organic phase was dried (MgSO4) the solvent was evaporated to give a residue that the mixture was heated at reflux overnight filtered the solvent was evaporated The residue was dissolved in diethyl ether (200 mL) the organic solution was washed with water (2×20 mL) dried (MgSO4) in the presence of activated carbon The mixture was filtered the solvent was evaporated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: tert-Butyl 4-(cyanomethyl)piperidine-1-carboxylate (91 mmol) was dissolved in ethanol (200 mL), and an aqueous hydroxylamine solution (50%, 17 mL, 170 mmol) was added, followed by heating to reflux for 3.5 hours. The reaction solution was cooled, and subsequently concentrated under reduced pressure to afford tert-butyl 4-[2-amino-2-(hydroxyimino)ethyl]piperidine-1-carboxylate as a colorless amorphous solid. by heating to reflux for 3.5 hours The reaction solution was cooled subsequently concentrated under reduced pressure