tert-butyl 4-[(4-aminophenyl)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:; See reaction.notes.procedure_details.

Procedure: 1-tert-Butoxycarbonyl-4-(4-aminobenzyl)piperidine (1.2 g, 4.15 mmol) was dissolved in tetrahydrofuran (20 mL). To the solution was added triethylamine (0.64 mL, 4.57 mmol). To the mixture was added dropwise methanesulfonyl chloride (0.39 mL, 4.95 mmol) under ice cooling, and the mixture was stirred under ice cooling for 30 minutes and at room temperature for 30 minutes. The reaction mixture was poured into ice-water (20 mL), and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=1/1) to give the titled compound (1.43 g) as colorless powdery crystals. the mixture was extracted with ethyl acetate The extract was washed with water and saturated sodium chloride solution dried over anhydrous magnesium sulfate concentrated under reduced pressure the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=1/1)

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

Procedure: 1-tert-Butoxycarbonyl-4-(4-aminobenzyl)piperidine (1 g, 3.45 mmol) was dissolved in 1-butanol (20 mL). To the solution were added bis(2-chloroethyl) ether (490 mg, 3.45 mmol) and potassium carbonate (1 g, 7.23 mmol), and the mixture was heated for 30 hours under reflux. The reaction mixture was poured into water (50 mL), and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=3/1) to give 1-tert-butoxycarbonyl-4-(4-morpholinobenzyl)piperidine (869 mg) as a colorless oily substance. This compound (859 mg, 2.39 mmol) was dissolved in ethyl acetate (10 mL). To the solution was added 4N-hydrogen chloride in ethyl acetate (5 mL), and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure to give the titled compound (562 mg) as colorless powders. the mixture was heated for 30 hours under reflux the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried over anhydrous magnesium sulfate concentrated under reduced pressure the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=3/1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-tert-butoxycarbonyl-4-(4-aminobenzyl)piperidine (1 g, 3.46 mmol) in acetic acid (14 mL) were added orthoethyl formate (2.4 mL, 20.7 mmol) and sodium azide (0.27 g, 4.13 mmol), and the mixture was stirred at room temperature for 30 minutes and at 80° C. for 2 hours. The mixture was cooled to room temperature. To the mixture were added water (20 mL) and a solution of sodium nitrite (4.3 g) in water (20 mL), and the mixture was stirred at room temperature for 10 minutes and extracted with ethyl acetate. The extract was washed with aqueous solution of sodium hydrogencarbonate and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3) to give 1-tert-butoxycarbonyl-4-[4-(1H-tetrazol-1-yl)benzyl]piperidine (950 mg) as colorless powdery crystals. This compound (950 mg, 2.78 mmol) was dissolved in ethyl acetate (10 mL). To the solution was added 4N-hydrogen chloride in ethyl acetate (10 mL), and the mixture was stirred at room temperature for 2 hours. The resulting crystals were collected by filtration, washed with ethyl acetate (5 mL) and dried to give the titled compound (697 mg) as colorless powdery crystals. The mixture was cooled to room temperature extracted with ethyl acetate The extract was washed with aqueous solution of sodium hydrogencarbonate and saturated sodium chloride solution dried over anhydrous magnesium sulfate concentrated under reduced pressure the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3)

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

Procedure: To the solution of 1-tert-butoxycarbonyl-4-(4-nitrobenzyl)piperidine (4.53 g, 14.2 mmol) in methanol-tetrahydrofuran (1:1, 100 mL) were added activated carbon (2 g) and anhydrous ferric chloride (250 mg). To the mixture was added hydrazine monohydrate (5.64 mL), and the mixture was heated for 26 hours under ref lux. The reaction mixture was cooled to room temperature, the activated carbon was filtered off. The activated carbon was washed with metahnol. The filtrate and washings were combined, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3) to give the titled compound (4 g) as colorless powdery crystals. the mixture was heated for 26 hours under ref lux the activated carbon was filtered off The activated carbon was washed with metahnol concentrated under reduced pressure The concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3)

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

Procedure: 1-tert-Butoxycarbonyl-4-(4-aminobenzyl)piperidine (1.2 g, 4.15 mmol) was dissolved in tetrahydrofuran (20 mL). To the solution was added triethylamine (0.64 mL, 4.57 mmol). To the mixture was added dropwise methanesulfonyl chloride (0.39 mL, 4.95 mmol) under ice cooling, and the mixture was stirred under ice cooling for 30 minutes and at room temperature for 30 minutes. The reaction mixture was poured into ice-water (20 mL), and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=1/1) to give the titled compound (1.43 g) as colorless powdery crystals. the mixture was extracted with ethyl acetate The extract was washed with water and saturated sodium chloride solution dried over anhydrous magnesium sulfate concentrated under reduced pressure the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=1/1)

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

Procedure: 1-tert-Butoxycarbonyl-4-(4-aminobenzyl)piperidine (1 g, 3.45 mmol) was dissolved in 1-butanol (20 mL). To the solution were added bis(2-chloroethyl) ether (490 mg, 3.45 mmol) and potassium carbonate (1 g, 7.23 mmol), and the mixture was heated for 30 hours under reflux. The reaction mixture was poured into water (50 mL), and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=3/1) to give 1-tert-butoxycarbonyl-4-(4-morpholinobenzyl)piperidine (869 mg) as a colorless oily substance. This compound (859 mg, 2.39 mmol) was dissolved in ethyl acetate (10 mL). To the solution was added 4N-hydrogen chloride in ethyl acetate (5 mL), and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure to give the titled compound (562 mg) as colorless powders. the mixture was heated for 30 hours under reflux the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried over anhydrous magnesium sulfate concentrated under reduced pressure the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=3/1)

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

Procedure: 1-tert-Butoxycarbonyl-4-(4-aminobenzyl)piperidine (1 g, 3.45 mmol) was dissolved in 1-butanol (20 mL). To the solution were added bis(2-chloroethyl) ether (490 mg, 3.45 mmol) and potassium carbonate (1 g, 7.23 mmol), and the mixture was heated for 30 hours under reflux. The reaction mixture was poured into water (50 mL), and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=3/1) to give 1-tert-butoxycarbonyl-4-(4-morpholinobenzyl)piperidine (869 mg) as a colorless oily substance. This compound (859 mg, 2.39 mmol) was dissolved in ethyl acetate (10 mL). To the solution was added 4N-hydrogen chloride in ethyl acetate (5 mL), and the mixture was stirred at room temperature for 2 hours. The solvent was distilled off under reduced pressure to give the titled compound (562 mg) as colorless powders. the mixture was heated for 30 hours under reflux the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried over anhydrous magnesium sulfate concentrated under reduced pressure the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=3/1)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-tert-butoxycarbonyl-4-(4-aminobenzyl)piperidine (1 g, 3.46 mmol) in acetic acid (14 mL) were added orthoethyl formate (2.4 mL, 20.7 mmol) and sodium azide (0.27 g, 4.13 mmol), and the mixture was stirred at room temperature for 30 minutes and at 80° C. for 2 hours. The mixture was cooled to room temperature. To the mixture were added water (20 mL) and a solution of sodium nitrite (4.3 g) in water (20 mL), and the mixture was stirred at room temperature for 10 minutes and extracted with ethyl acetate. The extract was washed with aqueous solution of sodium hydrogencarbonate and saturated sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3) to give 1-tert-butoxycarbonyl-4-[4-(1H-tetrazol-1-yl)benzyl]piperidine (950 mg) as colorless powdery crystals. This compound (950 mg, 2.78 mmol) was dissolved in ethyl acetate (10 mL). To the solution was added 4N-hydrogen chloride in ethyl acetate (10 mL), and the mixture was stirred at room temperature for 2 hours. The resulting crystals were collected by filtration, washed with ethyl acetate (5 mL) and dried to give the titled compound (697 mg) as colorless powdery crystals. The mixture was cooled to room temperature extracted with ethyl acetate The extract was washed with aqueous solution of sodium hydrogencarbonate and saturated sodium chloride solution dried over anhydrous magnesium sulfate concentrated under reduced pressure the concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3)

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

Procedure: To the solution of 1-tert-butoxycarbonyl-4-(4-nitrobenzyl)piperidine (4.53 g, 14.2 mmol) in methanol-tetrahydrofuran (1:1, 100 mL) were added activated carbon (2 g) and anhydrous ferric chloride (250 mg). To the mixture was added hydrazine monohydrate (5.64 mL), and the mixture was heated for 26 hours under ref lux. The reaction mixture was cooled to room temperature, the activated carbon was filtered off. The activated carbon was washed with metahnol. The filtrate and washings were combined, and concentrated under reduced pressure. The concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3) to give the titled compound (4 g) as colorless powdery crystals. the mixture was heated for 26 hours under ref lux the activated carbon was filtered off The activated carbon was washed with metahnol concentrated under reduced pressure The concentrate was purified by silica gel column chromatography (hexane/ethyl acetate=2/3)

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