tert-butyl N-[(4-hydroxypiperidin-4-yl)methyl]carbamate

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

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-1-phenyl-1-hexanone (2.9 g) and potassium carbonate (3 g) were added to a solution of 4-hydroxy-4-tert-butoxycarbonylaminomethylpiperidine (2.5 g) in dimethylformamide (40 ml), and the mixture was stirred at 60° C. for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with brine, dried and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=10:1) to give 3.74 g of 4-hydroxy-1-(6-oxo-6-phenylhexyl)-4-tert-butoxycarbonylaminomethylpiperidine. the mixture was extracted with chloroform The organic layer was washed with brine dried the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (chloroform:methanol=10:1)

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

Procedure: The title compound was prepared by a method similar to that shown in the Step 2 of Example 3 by using tert-butyl [(4-hydroxypiperidin-4-yl)methyl]carbamate (Chem. Pharm. Bull., 2002, 50 (9) 1187-1194) and methyl 1-(iodomethyl)cyclohexanecarboxylate (Step 1 of Example 6).

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-1-phenyl-1-hexanone (2.9 g) and potassium carbonate (3 g) were added to a solution of 4-hydroxy-4-tert-butoxycarbonylaminomethylpiperidine (2.5 g) in dimethylformamide (40 ml), and the mixture was stirred at 60° C. for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with brine, dried and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=10:1) to give 3.74 g of 4-hydroxy-1-(6-oxo-6-phenylhexyl)-4-tert-butoxycarbonylaminomethylpiperidine. the mixture was extracted with chloroform The organic layer was washed with brine dried the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (chloroform:methanol=10:1)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Bromo-1-phenyl-1-hexanone (2.9 g) and potassium carbonate (3 g) were added to a solution of 4-hydroxy-4-tert-butoxycarbonylaminomethylpiperidine (2.5 g) in dimethylformamide (40 ml), and the mixture was stirred at 60° C. for 2 hr. Water was added to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with brine, dried and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (chloroform:methanol=10:1) to give 3.74 g of 4-hydroxy-1-(6-oxo-6-phenylhexyl)-4-tert-butoxycarbonylaminomethylpiperidine. the mixture was extracted with chloroform The organic layer was washed with brine dried the solvent was evaporated under reduced pressure The obtained residue was purified by silica gel column chromatography (chloroform:methanol=10:1)

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

Procedure: To a suspension in isoamyl alcohol (35 ml) of conventionally known compounds: 4-[(t-butoxycarbonylamino)methyl]-4-hydroxypiperidine (2.00 g) and 4-chloropyridine 1-oxide (1.12 g), was added sodium hydrogencarbonate (1.75 g) and the mixture was heated under reflux for 4 hours. The reaction mixture was allowed to cool and water was added thereto. The reaction mixture was extracted with methylene chloride and the organic layer was washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent:methylene chloride:methanol=9:1-4:1) to obtain the title compound (1.03 g). the mixture was heated under reflux for 4 hours to cool The reaction mixture was extracted with methylene chloride the organic layer was washed with saturated sodium chloride solution dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified by silica gel column chromatography (eluent:methylene chloride:methanol=9:1-4:1)

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

Procedure: The title compound was prepared by a method similar to that shown in the Step 2 of Example 3 by using tert-butyl [(4-hydroxypiperidin-4-yl)methyl]carbamate (Chem. Pharm. Bull., 2002, 50 (9) 1187-1194) and methyl 1-(iodomethyl)cyclohexanecarboxylate (Step 1 of Example 6).

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

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

Procedure: To a suspension in isoamyl alcohol (35 ml) of conventionally known compounds: 4-[(t-butoxycarbonylamino)methyl]-4-hydroxypiperidine (2.00 g) and 4-chloropyridine 1-oxide (1.12 g), was added sodium hydrogencarbonate (1.75 g) and the mixture was heated under reflux for 4 hours. The reaction mixture was allowed to cool and water was added thereto. The reaction mixture was extracted with methylene chloride and the organic layer was washed with saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and the resulting residue was purified by silica gel column chromatography (eluent:methylene chloride:methanol=9:1-4:1) to obtain the title compound (1.03 g). the mixture was heated under reflux for 4 hours to cool The reaction mixture was extracted with methylene chloride the organic layer was washed with saturated sodium chloride solution dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the resulting residue was purified by silica gel column chromatography (eluent:methylene chloride:methanol=9:1-4:1)

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

Procedure: The title compound was prepared by a method similar to that shown in the Step 2 of Example 3 by using tert-butyl [(4-hydroxypiperidin-4-yl)methyl]carbamate (Chem. Pharm. Bull., 2002, 50 (9) 1187-1194) and methyl 1-(iodomethyl)cyclohexanecarboxylate (Step 1 of Example 6).

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

Procedure: According to the same procedure described in Example 101, starting with the compound prepared in Example 251 instead of the compound prepared in Example 226 and the compound prepared in Example 139 instead of 2-phenylthiazole-5-carbaldehyde, the title compound having the following physical data was obtained.

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

Procedure: A solution the compound prepared in Example 250 (0.68 g) in ethanol (11 mL) was treated with hydrazine monohydrate (0.208 mL), followed by 10% palladium-carbon (0.238 g). The mixture was refluxed for 18 hours. After allowing mixture to cool to room temperature, the catalyst was filtered off and washed with methanol. The filtrate was evaporated in vacuo to obtain the title compound (0.510 g) having the following physical data. The mixture was refluxed for 18 hours the catalyst was filtered off washed with methanol The filtrate was evaporated in vacuo