tert-butyl N-(3-chloropropyl)carbamate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a solution of N-Boc-3-chloropropylamine (10.0 g, 51.8 mmol) in THF was added sodium hydride (1.87 g, 78 mmol). After 20 min, benzyl bromide (9.24 mL, 78 mmol) was added and the reaction mixture was heated at reflux for 16 h. After cooling, the reaction mixture was diluted with Et2O (150 mL) and H2O (50 mL), the layers were separated and the aqueous layer was extracted twice with Et2O. The combined organic phases were washed with H2O and brine, dried (MgSO4), filtered and concentrated. The resulting yellow oil was purified by flash chromatography (SiO2, 10% EtOAc-hexane) to give N-Boc-N-benzyl-3-chloropropylamine (1.97 g, 13% yield) as a pale yellow oil. the reaction mixture was heated at reflux for 16 h After cooling the layers were separated the aqueous layer was extracted twice with Et2O The combined organic phases were washed with H2O and brine dried (MgSO4) filtered concentrated The resulting yellow oil was purified by flash chromatography (SiO2, 10% EtOAc-hexane)

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

実験手順: To a solution of N-Boc-3-chloropropylamine (10.0 g, 51.8 mmol) in THF was added sodium hydride (1.87 g, 78 mmol). After 20 min, benzyl bromide (9.24 mL, 78 mmol) was added and the reaction mixture was heated at reflux for 16 h. After cooling, the reaction mixture was diluted with Et2O (150 mL) and H2O (50 mL), the layers were separated and the aqueous layer was extracted twice with Et2O. The combined organic phases were washed with H2O and brine, dried (MgSO4), filtered and concentrated. The resulting yellow oil was purified by flash chromatography (SiO2, 10% EtOAc-hexane) to give N-Boc-N-benzyl-3-chloropropylamine (1.97 g, 13% yield) as a pale yellow oil. the reaction mixture was heated at reflux for 16 h After cooling the layers were separated the aqueous layer was extracted twice with Et2O The combined organic phases were washed with H2O and brine dried (MgSO4) filtered concentrated The resulting yellow oil was purified by flash chromatography (SiO2, 10% EtOAc-hexane)

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

実験手順: To a solution of N-Boc-3-chloropropylamine (10.0 g, 51.8 mmol) in THF was added sodium hydride (1.87 g, 78 mmol). After 20 min, benzyl bromide (9.24 mL, 78 mmol) was added and the reaction mixture was heated at reflux for 16 h. After cooling, the reaction mixture was diluted with Et2O (150 mL) and H2O (50 mL), the layers were separated and the aqueous layer was extracted twice with Et2O. The combined organic phases were washed with H2O and brine, dried (MgSO4), filtered and concentrated. The resulting yellow oil was purified by flash chromatography (SiO2, 10% EtOAc-hexane) to give N-Boc-N-benzyl-3-chloropropylamine (1.97 g, 13% yield) as a pale yellow oil. the reaction mixture was heated at reflux for 16 h After cooling the layers were separated the aqueous layer was extracted twice with Et2O The combined organic phases were washed with H2O and brine dried (MgSO4) filtered concentrated The resulting yellow oil was purified by flash chromatography (SiO2, 10% EtOAc-hexane)

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: This compound, employed as the starting material in example 2, is prepared by following substantially the same procedure described above under (a) but using 4-chloro-butylamine hydrochloride instead of 3-chloro-propylamine hydrochloride. is prepared

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 4.0 g (12.7 mmol) of 1-amino-7-hydroxyisoquinoline monohydrobromide was dissolved in 50 ml of DMF. 4.42 g (18.6 mmol) of t-butyl (3-chloropropyl)carbamate, 8.76 g (63.5 mmol) of potassium carbonate and 4.69 g (12.7 mmol) of tetrabutylammonium iodide were added to the obtained solution, and they were stirred at 70° C. for 3 days. After the treatment with dichloromethane as the extraction solvent in an ordinary manner, the crude product was obtained, which was then purified by the silica gel column chromatography to obtain the title compound. which was then purified by the silica gel column chromatography

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

実験手順: 4.0 g (12.7 mmol) of 1-amino-7-hydroxyisoquinoline monohydrobromide was dissolved in 50 ml of DMF. 4.42 g (18.6 mmol) of t-butyl (3-chloropropyl)carbamate, 8.76 g (63.5 mmol) of potassium carbonate and 4.69 g (12.7 mmol) of tetrabutylammonium iodide were added to the obtained solution, and they were stirred at 70° C. for 3 days. After the treatment with dichloromethane as the extraction solvent in an ordinary manner, the crude product was obtained, which was then purified by the silica gel column chromatography to obtain the title compound. which was then purified by the silica gel column chromatography

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

実験手順: A mixture of 3.8 g (12.88 mmol) ethyl 7-bromo-3-hydroxynaphthalen-2-carboxylate, 3.0 g (15.5 mmol) 1-(tert.-butoxycarbonylamino)-3-chloropropane (prepared according to Helv. Chim. Acta 76 (1993), 1644), 2.0 g (14.5 mmol) potassium carbonate, and a catalytic amount of potassium iodide in 20 ml dry DMF was stirred at 90° C. for 6 h. It was poured into water, extracted three times with ethyl acetate, and the combined organic layers were washed three times with water, dried over sodium sulfate, and concentrated in vacuo. The intermediate was purified by chromatography on silica gel with toluene/acetone 9:1 to give 5.8 g (100%) of a yellow oil, which solidified rapidly upon standing. extracted three times with ethyl acetate the combined organic layers were washed three times with water dried over sodium sulfate concentrated in vacuo The intermediate was purified by chromatography on silica gel with toluene/acetone 9:1

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The compound of the title, employed as the starting material in example 1, is prepared by slowly adding a solution of 3-chloro-propylamine hydrochloride (12.98 g, 0.1 mol) in dioxane/water (100 ml 2/1 v/v) to a vigorously stirred mixture of di-(tert-butyl)carbonate (24 g, 0.11 mol), 1N Na2CO3 (100 ml) and dioxane/water (200 ml, 2/1 v/v) cooled to 0° C. When the addition is over, the reaction mixture is stirred at room temperature for an additional hour, dioxane is removed under vacuum and the aqueous phase is extracted a few times with ethyl acetate. is prepared When the addition dioxane is removed under vacuum the aqueous phase is extracted a few times with ethyl acetate