3-(2-methylpropoxy)azetidine;hydrochloride

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

実験手順: 3-Isobutoxyazetidine hydrochloride (98 mg, 0.6 mmol), EDCI (113 mg, 0.6 mmol), HOBt (80 mg, 0.6 mmol) and diisopropylethylamine (170 μL, 1.0 mmol) were successively added to a solution of 3-(chloromethyl)-1-methyl-1H-pyrazole (100 mg, 0.4 mmol) in dimethylormamide (10 mL) at room temperature. The reaction mixture was stirred over a week-end and then diluted by addition ethyl acetate (20 mL) and water (2×20 mL). The aqueous layer was separated and extracted with ethyl acetate (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (98:2 to 92:8) as eluent. The title product was obtained as a white solid (40 mg, 31%). The aqueous layer was separated extracted with ethyl acetate (2×20 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloroethyl chloroformate (83 μL, 0.77 mmol) was added to a solution of 1-benzhydryl-3-isobutoxyazetidine (175 mg, 0.60 mmol) in 1,2-dichloroethane (3 mL) at room temperature. The reaction mixture was then heated up to 70° C. and stirred for 1.5 hours. After cooling down to room temperature, methanol (3 mL) was added and the reaction mixture was heated again to 70° C. and stirred for an additional 1.5 hours. After concentration to dryness, the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (98 mg, quantitative) which was used in the next step without further purification. After cooling down to room temperature the reaction mixture was heated again to 70° C. stirred for an additional 1.5 hours After concentration to dryness the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (98 mg, quantitative) which was used in the next step without further purification

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloroethyl chloroformate (83 μL, 0.77 mmol) was added to a solution of 1-benzhydryl-3-isobutoxyazetidine (175 mg, 0.60 mmol) in 1,2-dichloroethane (3 mL) at room temperature. The reaction mixture was then heated up to 70° C. and stirred for 1.5 hours. After cooling down to room temperature, methanol (3 mL) was added and the reaction mixture was heated again to 70° C. and stirred for an additional 1.5 hours. After concentration to dryness, the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (98 mg, quantitative) which was used in the next step without further purification. After cooling down to room temperature the reaction mixture was heated again to 70° C. stirred for an additional 1.5 hours After concentration to dryness the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (98 mg, quantitative) which was used in the next step without further purification

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

実験手順: 3-Isobutoxyazetidine hydrochloride (98 mg, 0.6 mmol), EDCI (113 mg, 0.6 mmol), HOBt (80 mg, 0.6 mmol) and diisopropylethylamine (170 μL, 1.0 mmol) were successively added to a solution of 3-(chloromethyl)-1-methyl-1H-pyrazole (100 mg, 0.4 mmol) in dimethylormamide (10 mL) at room temperature. The reaction mixture was stirred over a week-end and then diluted by addition ethyl acetate (20 mL) and water (2×20 mL). The aqueous layer was separated and extracted with ethyl acetate (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (98:2 to 92:8) as eluent. The title product was obtained as a white solid (40 mg, 31%). The aqueous layer was separated extracted with ethyl acetate (2×20 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloroethyl chloroformate (83 μL, 0.77 mmol) was added to a solution of 1-benzhydryl-3-isobutoxyazetidine (175 mg, 0.60 mmol) in 1,2-dichloroethane (3 mL) at room temperature. The reaction mixture was then heated up to 70° C. and stirred for 1.5 hours. After cooling down to room temperature, methanol (3 mL) was added and the reaction mixture was heated again to 70° C. and stirred for an additional 1.5 hours. After concentration to dryness, the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (98 mg, quantitative) which was used in the next step without further purification. After cooling down to room temperature the reaction mixture was heated again to 70° C. stirred for an additional 1.5 hours After concentration to dryness the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (98 mg, quantitative) which was used in the next step without further purification

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

実験手順: 3-Isobutoxyazetidine hydrochloride (98 mg, 0.6 mmol), EDCI (113 mg, 0.6 mmol), HOBt (80 mg, 0.6 mmol) and diisopropylethylamine (170 μL, 1.0 mmol) were successively added to a solution of 3-(chloromethyl)-1-methyl-1H-pyrazole (100 mg, 0.4 mmol) in dimethylormamide (10 mL) at room temperature. The reaction mixture was stirred over a week-end and then diluted by addition ethyl acetate (20 mL) and water (2×20 mL). The aqueous layer was separated and extracted with ethyl acetate (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (98:2 to 92:8) as eluent. The title product was obtained as a white solid (40 mg, 31%). The aqueous layer was separated extracted with ethyl acetate (2×20 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloroethyl chloroformate (83 μL, 0.77 mmol) was added to a solution of 1-benzhydryl-3-isobutoxyazetidine (175 mg, 0.60 mmol) in 1,2-dichloroethane (3 mL) at room temperature. The reaction mixture was then heated up to 70° C. and stirred for 1.5 hours. After cooling down to room temperature, methanol (3 mL) was added and the reaction mixture was heated again to 70° C. and stirred for an additional 1.5 hours. After concentration to dryness, the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (98 mg, quantitative) which was used in the next step without further purification. After cooling down to room temperature the reaction mixture was heated again to 70° C. stirred for an additional 1.5 hours After concentration to dryness the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (98 mg, quantitative) which was used in the next step without further purification

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

実験手順: 3-Isobutoxyazetidine hydrochloride (98 mg, 0.6 mmol), EDCI (113 mg, 0.6 mmol), HOBt (80 mg, 0.6 mmol) and diisopropylethylamine (170 μL, 1.0 mmol) were successively added to a solution of 3-(chloromethyl)-1-methyl-1H-pyrazole (100 mg, 0.4 mmol) in dimethylormamide (10 mL) at room temperature. The reaction mixture was stirred over a week-end and then diluted by addition ethyl acetate (20 mL) and water (2×20 mL). The aqueous layer was separated and extracted with ethyl acetate (2×20 mL). The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (98:2 to 92:8) as eluent. The title product was obtained as a white solid (40 mg, 31%). The aqueous layer was separated extracted with ethyl acetate (2×20 mL) The combined organic phases were washed with a saturated solution of sodium chloride (3×20 mL) dried over sodium sulfate filtered concentrated to dryness The residue was purified by chromatography on silica gel

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 1-Chloroethyl chloroformate (83 μL, 0.77 mmol) was added to a solution of 1-benzhydryl-3-isobutoxyazetidine (175 mg, 0.60 mmol) in 1,2-dichloroethane (3 mL) at room temperature. The reaction mixture was then heated up to 70° C. and stirred for 1.5 hours. After cooling down to room temperature, methanol (3 mL) was added and the reaction mixture was heated again to 70° C. and stirred for an additional 1.5 hours. After concentration to dryness, the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (98 mg, quantitative) which was used in the next step without further purification. After cooling down to room temperature the reaction mixture was heated again to 70° C. stirred for an additional 1.5 hours After concentration to dryness the crude mixture was triturated in pentane (2×5 mL) to give a yellow oil (98 mg, quantitative) which was used in the next step without further purification