tert-butyl 4-[(4-aminophenoxy)methyl]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:

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

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 1-tert-butyloxycarbonyl-4-[(4-aminophenyloxy)methyl]piperidine (0.75 g) obtained in Example 13 were added dimethylformamide (10 ml), potassium carbonate (1.4 g) and dibromobutane (0.54 g) and the mixture was heated to 70° C. and stirred overnight. To the reaction solution was added water which was extracted with ethyl acetate (50 ml×3). The combined extract was dried over sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=5/1 (v/v)) to obtain 1-tert-butyloxycarbonyl-4-[(4-pyrrolidinophenyloxy)methyl]piperidine (0.55 g) as colorless crystals, m.p. 141°-145° C. was extracted with ethyl acetate (50 ml×3) The combined extract was dried over sodium sulfate concentrated under reduced pressure The residue thus obtained was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=5/1 (v/v))

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

Procedure: 1-tert-Butyloxycarbonyl-4-[(4-nitrophenyloxy)methyl]piperidine (1.9 g) was dissolved in ethanol (40 ml) and to the mixture was added conc. hydrochloric acid (0.5 ml). By using 10% palladium/carbon as a catalyst, catalytic reduction was conducted at normal pressure and room temperature overnight. After completion of the reaction, the catalyst was removed by filtration and the filtrate was concentrated under reduced pressure. The concentrate was diluted with methylene chloride and washed with aqueous saturated solution of sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1 (v/v)) to obtain 1-tert-butyloxycarbonyl-4-[(4-aminophenyloxy)methyl]piperidine (1.0 g) as white crystals, m.p. 100°-101° C. was conducted at normal pressure and room temperature overnight After completion of the reaction the catalyst was removed by filtration the filtrate was concentrated under reduced pressure The concentrate was diluted with methylene chloride washed with aqueous saturated solution of sodium bicarbonate The organic layer was dried over sodium sulfate concentrated under reduced pressure The residue thus obtained was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1 (v/v))

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 1-tert-butyloxycarbonyl-4-[(4-aminophenyloxy)methyl]piperidine (0.75 g) obtained in Example 13 were added dimethylformamide (10 ml), potassium carbonate (1.4 g) and dibromobutane (0.54 g) and the mixture was heated to 70° C. and stirred overnight. To the reaction solution was added water which was extracted with ethyl acetate (50 ml×3). The combined extract was dried over sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=5/1 (v/v)) to obtain 1-tert-butyloxycarbonyl-4-[(4-pyrrolidinophenyloxy)methyl]piperidine (0.55 g) as colorless crystals, m.p. 141°-145° C. was extracted with ethyl acetate (50 ml×3) The combined extract was dried over sodium sulfate concentrated under reduced pressure The residue thus obtained was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=5/1 (v/v))

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

Procedure: 1-tert-Butyloxycarbonyl-4-[(4-nitrophenyloxy)methyl]piperidine (1.9 g) was dissolved in ethanol (40 ml) and to the mixture was added conc. hydrochloric acid (0.5 ml). By using 10% palladium/carbon as a catalyst, catalytic reduction was conducted at normal pressure and room temperature overnight. After completion of the reaction, the catalyst was removed by filtration and the filtrate was concentrated under reduced pressure. The concentrate was diluted with methylene chloride and washed with aqueous saturated solution of sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1 (v/v)) to obtain 1-tert-butyloxycarbonyl-4-[(4-aminophenyloxy)methyl]piperidine (1.0 g) as white crystals, m.p. 100°-101° C. was conducted at normal pressure and room temperature overnight After completion of the reaction the catalyst was removed by filtration the filtrate was concentrated under reduced pressure The concentrate was diluted with methylene chloride washed with aqueous saturated solution of sodium bicarbonate The organic layer was dried over sodium sulfate concentrated under reduced pressure The residue thus obtained was purified by silica gel column chromatography (developing solvent: hexane/ethyl acetate=1/1 (v/v))