1-[(4-methoxyphenyl)methyl]piperidin-4-ol

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

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

Procedure: To a stirred solution of 1-(4-methoxybenzyl)piperidin-4-ol (0.33 g, 1.49 mmol) in toluene (10 mL) at room temperature was added triphenylphosphine (0.44 g, 1.67 mmol) and methyl 3-chloro-4-hydroxybenzoate (0.42 g, 2.25 mmol). The reaction was stirred at room temperature for 5 min. After this time, diisopropyl azodicarboxylate (0.33 g, 1.67 mmol) was added dropwise and the reaction was stirred at room temperature overnight. The mixture was concentrated under reduced pressure and the resulting residue was purified by flash chromatography (silica gel, methylene chloride/methanol/30% ammonium hydroxide=25/1/0.05) to afford methyl 3-chloro-4-(1-(4-methoxybenzyl)piperidin-4-yloxy)benzoate as a white solid (0.05 g, 10%). MS (ESI): 390.1 (M+1). the reaction was stirred at room temperature overnight The mixture was concentrated under reduced pressure the resulting residue was purified by flash chromatography (silica gel, methylene chloride/methanol/30% ammonium hydroxide=25/1/0.05)

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

Procedure: To a stirred solution of 4-hydroxypiperidine (0.97 g, 9.60 mmol) in anhydrous dimethylformamide (20 mL) at 0° C. was added 1-(bromomethyl)-4-methoxybenzene (1.93 g, 9.60 mmol) and triethylamine (2.16 g, 21.4 mmol). The reaction mixture was then warmed to room temperature and stirred overnight. After this time the mixture was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (40 mL), washed with water (20 mL), then brine (20 mL) and dried over sodium sulfate. The drying agent was filtered off and the filtrate concentrated under reduced pressure. The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride) to afford 1-(4-methoxybenzyl)piperidin-4-ol as a brown oil (1.70 g, 80%). 1H-NMR (CDCl3, 300 MHz): δ 7.27 (d, J=7.8 Hz, 2H), 6.86 (d, J=7.8 Hz, 2H), 3.79 (s, 3H), 3.76 (m, 1H), 3.55 (s, 2H), 2.81 (m, 2H), 2.29 (m, 2H), 1.96 (m, 2H), 1.64 (m, 3H); MS (ESI): 222.1 (M+H). After this time the mixture was concentrated under reduced pressure the resulting residue was dissolved in ethyl acetate (40 mL) washed with water (20 mL) brine (20 mL) and dried over sodium sulfate The drying agent was filtered off the filtrate concentrated under reduced pressure The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride)

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

Procedure: To a stirred solution of 4-hydroxypiperidine (0.97 g, 9.60 mmol) in anhydrous dimethylformamide (20 mL) at 0° C. was added 1-(bromomethyl)-4-methoxybenzene (1.93 g, 9.60 mmol) and triethylamine (2.16 g, 21.4 mmol). The reaction mixture was then warmed to room temperature and stirred overnight. After this time the mixture was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (40 mL), washed with water (20 mL), then brine (20 mL) and dried over sodium sulfate. The drying agent was filtered off and the filtrate concentrated under reduced pressure. The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride) to afford 1-(4-methoxybenzyl)piperidin-4-ol as a brown oil (1.70 g, 80%). 1H-NMR (CDCl3, 300 MHz): δ 7.27 (d, J=7.8 Hz, 2H), 6.86 (d, J=7.8 Hz, 2H), 3.79 (s, 3H), 3.76 (m, 1H), 3.55 (s, 2H), 2.81 (m, 2H), 2.29 (m, 2H), 1.96 (m, 2H), 1.64 (m, 3H); MS (ESI): 222.1 (M+H). After this time the mixture was concentrated under reduced pressure the resulting residue was dissolved in ethyl acetate (40 mL) washed with water (20 mL) brine (20 mL) and dried over sodium sulfate The drying agent was filtered off the filtrate concentrated under reduced pressure The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride)

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

Procedure: To a stirred solution of 1-(4-methoxybenzyl)piperidin-4-ol (0.33 g, 1.49 mmol) in toluene (10 mL) at room temperature was added triphenylphosphine (0.44 g, 1.67 mmol) and methyl 3-chloro-4-hydroxybenzoate (0.42 g, 2.25 mmol). The reaction was stirred at room temperature for 5 min. After this time, diisopropyl azodicarboxylate (0.33 g, 1.67 mmol) was added dropwise and the reaction was stirred at room temperature overnight. The mixture was concentrated under reduced pressure and the resulting residue was purified by flash chromatography (silica gel, methylene chloride/methanol/30% ammonium hydroxide=25/1/0.05) to afford methyl 3-chloro-4-(1-(4-methoxybenzyl)piperidin-4-yloxy)benzoate as a white solid (0.05 g, 10%). MS (ESI): 390.1 (M+1). the reaction was stirred at room temperature overnight The mixture was concentrated under reduced pressure the resulting residue was purified by flash chromatography (silica gel, methylene chloride/methanol/30% ammonium hydroxide=25/1/0.05)

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

Procedure: To a stirred solution of 4-hydroxypiperidine (0.97 g, 9.60 mmol) in anhydrous dimethylformamide (20 mL) at 0° C. was added 1-(bromomethyl)-4-methoxybenzene (1.93 g, 9.60 mmol) and triethylamine (2.16 g, 21.4 mmol). The reaction mixture was then warmed to room temperature and stirred overnight. After this time the mixture was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (40 mL), washed with water (20 mL), then brine (20 mL) and dried over sodium sulfate. The drying agent was filtered off and the filtrate concentrated under reduced pressure. The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride) to afford 1-(4-methoxybenzyl)piperidin-4-ol as a brown oil (1.70 g, 80%). 1H-NMR (CDCl3, 300 MHz): δ 7.27 (d, J=7.8 Hz, 2H), 6.86 (d, J=7.8 Hz, 2H), 3.79 (s, 3H), 3.76 (m, 1H), 3.55 (s, 2H), 2.81 (m, 2H), 2.29 (m, 2H), 1.96 (m, 2H), 1.64 (m, 3H); MS (ESI): 222.1 (M+H). After this time the mixture was concentrated under reduced pressure the resulting residue was dissolved in ethyl acetate (40 mL) washed with water (20 mL) brine (20 mL) and dried over sodium sulfate The drying agent was filtered off the filtrate concentrated under reduced pressure The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride)

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

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

Procedure: To a stirred solution of 1-(4-methoxybenzyl)piperidin-4-ol (0.33 g, 1.49 mmol) in toluene (10 mL) at room temperature was added triphenylphosphine (0.44 g, 1.67 mmol) and methyl 3-chloro-4-hydroxybenzoate (0.42 g, 2.25 mmol). The reaction was stirred at room temperature for 5 min. After this time, diisopropyl azodicarboxylate (0.33 g, 1.67 mmol) was added dropwise and the reaction was stirred at room temperature overnight. The mixture was concentrated under reduced pressure and the resulting residue was purified by flash chromatography (silica gel, methylene chloride/methanol/30% ammonium hydroxide=25/1/0.05) to afford methyl 3-chloro-4-(1-(4-methoxybenzyl)piperidin-4-yloxy)benzoate as a white solid (0.05 g, 10%). MS (ESI): 390.1 (M+1). the reaction was stirred at room temperature overnight The mixture was concentrated under reduced pressure the resulting residue was purified by flash chromatography (silica gel, methylene chloride/methanol/30% ammonium hydroxide=25/1/0.05)

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

Procedure: To a stirred solution of 1-(4-methoxybenzyl)piperidin-4-ol (0.33 g, 1.49 mmol) in toluene (10 mL) at room temperature was added triphenylphosphine (0.44 g, 1.67 mmol) and methyl 3-chloro-4-hydroxybenzoate (0.42 g, 2.25 mmol). The reaction was stirred at room temperature for 5 min. After this time, diisopropyl azodicarboxylate (0.33 g, 1.67 mmol) was added dropwise and the reaction was stirred at room temperature overnight. The mixture was concentrated under reduced pressure and the resulting residue was purified by flash chromatography (silica gel, methylene chloride/methanol/30% ammonium hydroxide=25/1/0.05) to afford methyl 3-chloro-4-(1-(4-methoxybenzyl)piperidin-4-yloxy)benzoate as a white solid (0.05 g, 10%). MS (ESI): 390.1 (M+1). the reaction was stirred at room temperature overnight The mixture was concentrated under reduced pressure the resulting residue was purified by flash chromatography (silica gel, methylene chloride/methanol/30% ammonium hydroxide=25/1/0.05)

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

Procedure: To a stirred solution of 4-hydroxypiperidine (0.97 g, 9.60 mmol) in anhydrous dimethylformamide (20 mL) at 0° C. was added 1-(bromomethyl)-4-methoxybenzene (1.93 g, 9.60 mmol) and triethylamine (2.16 g, 21.4 mmol). The reaction mixture was then warmed to room temperature and stirred overnight. After this time the mixture was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (40 mL), washed with water (20 mL), then brine (20 mL) and dried over sodium sulfate. The drying agent was filtered off and the filtrate concentrated under reduced pressure. The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride) to afford 1-(4-methoxybenzyl)piperidin-4-ol as a brown oil (1.70 g, 80%). 1H-NMR (CDCl3, 300 MHz): δ 7.27 (d, J=7.8 Hz, 2H), 6.86 (d, J=7.8 Hz, 2H), 3.79 (s, 3H), 3.76 (m, 1H), 3.55 (s, 2H), 2.81 (m, 2H), 2.29 (m, 2H), 1.96 (m, 2H), 1.64 (m, 3H); MS (ESI): 222.1 (M+H). After this time the mixture was concentrated under reduced pressure the resulting residue was dissolved in ethyl acetate (40 mL) washed with water (20 mL) brine (20 mL) and dried over sodium sulfate The drying agent was filtered off the filtrate concentrated under reduced pressure The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride)

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

Procedure: To a stirred solution of 4-hydroxypiperidine (0.97 g, 9.60 mmol) in anhydrous dimethylformamide (20 mL) at 0° C. was added 1-(bromomethyl)-4-methoxybenzene (1.93 g, 9.60 mmol) and triethylamine (2.16 g, 21.4 mmol). The reaction mixture was then warmed to room temperature and stirred overnight. After this time the mixture was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (40 mL), washed with water (20 mL), then brine (20 mL) and dried over sodium sulfate. The drying agent was filtered off and the filtrate concentrated under reduced pressure. The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride) to afford 1-(4-methoxybenzyl)piperidin-4-ol as a brown oil (1.70 g, 80%). 1H-NMR (CDCl3, 300 MHz): δ 7.27 (d, J=7.8 Hz, 2H), 6.86 (d, J=7.8 Hz, 2H), 3.79 (s, 3H), 3.76 (m, 1H), 3.55 (s, 2H), 2.81 (m, 2H), 2.29 (m, 2H), 1.96 (m, 2H), 1.64 (m, 3H); MS (ESI): 222.1 (M+H). After this time the mixture was concentrated under reduced pressure the resulting residue was dissolved in ethyl acetate (40 mL) washed with water (20 mL) brine (20 mL) and dried over sodium sulfate The drying agent was filtered off the filtrate concentrated under reduced pressure The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride)

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

Procedure: To a stirred solution of 4-hydroxypiperidine (0.97 g, 9.60 mmol) in anhydrous dimethylformamide (20 mL) at 0° C. was added 1-(bromomethyl)-4-methoxybenzene (1.93 g, 9.60 mmol) and triethylamine (2.16 g, 21.4 mmol). The reaction mixture was then warmed to room temperature and stirred overnight. After this time the mixture was concentrated under reduced pressure and the resulting residue was dissolved in ethyl acetate (40 mL), washed with water (20 mL), then brine (20 mL) and dried over sodium sulfate. The drying agent was filtered off and the filtrate concentrated under reduced pressure. The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride) to afford 1-(4-methoxybenzyl)piperidin-4-ol as a brown oil (1.70 g, 80%). 1H-NMR (CDCl3, 300 MHz): δ 7.27 (d, J=7.8 Hz, 2H), 6.86 (d, J=7.8 Hz, 2H), 3.79 (s, 3H), 3.76 (m, 1H), 3.55 (s, 2H), 2.81 (m, 2H), 2.29 (m, 2H), 1.96 (m, 2H), 1.64 (m, 3H); MS (ESI): 222.1 (M+H). After this time the mixture was concentrated under reduced pressure the resulting residue was dissolved in ethyl acetate (40 mL) washed with water (20 mL) brine (20 mL) and dried over sodium sulfate The drying agent was filtered off the filtrate concentrated under reduced pressure The residue obtained was purified by flash chromatography (silica gel, 0-5% methanol/methylene chloride)