5-bromo-N-ethylpentanamide

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Triphenylphosphine (2.88 g, 11 mmol, 1.1 eq.) was added to a solution of 5-bromo-N-ethylpentanamide 95 (2.08 g, 10 mmol, 1 eq.) in MeCN (5 ml) and the mixture was stirred for 14 h at 80° C. The mixture was allowed to cool to r.t. and concentrated under vacuum. The residue was added dropwise into Et2O (100 ml) and stirred vigorously for 10 min. The resulting solid was filtered, washed with Et2O (2×10 ml) and dissolved in CH2Cl2 (15 ml). This solution was then added dropwise into Et2O (200 ml) and stirred for 10 min. Solids were filtered, washed with Et2O (2×10 ml) and dried under high vacuum to give the title product 96 as a white powder (3.87 g, 82%). to cool to r.t. concentrated under vacuum The residue was added dropwise into Et2O (100 ml) stirred vigorously for 10 min The resulting solid was filtered washed with Et2O (2×10 ml) dissolved in CH2Cl2 (15 ml) This solution was then added dropwise into Et2O (200 ml) stirred for 10 min Solids were filtered washed with Et2O (2×10 ml) dried under high vacuum

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dimethylformamide (116 μL, 1.5 mmol, 0.1 eq.) and thionyl chloride (1.63 ml, 22.5 mmol, 1.5 eq.) were added to a solution of 5-bromovaleric acid (2.71 g, 15 mmol, 1 eq.) in toluene (20 ml) and the reaction mixture was stirred at 50° C. for 4 h. The volatiles were removed under high vacuum, THF (130 ml) was added and the mixture was cooled to 0° C. N,N-Diisopropylethylamine (4.2 ml, 24 mmol, 1.6 eq.) and ethylamine (2 M solution in THF, 9.0 ml, 18 mmol, 1.2 eq.) were added dropwise. The reaction mixture was stirred for 1 h at 0° C. before being quenched by the addition of saturated aq. NH4Cl (100 ml). The reaction mixture was extracted with Et2O (4×75 ml) and the combined organic phases were washed with brine (100 ml) before being dried (MgSO4), filtered, and concentrated to give the crude material. This was purified by flash chromatography, eluting with petrol/EtOAc (4:6), giving the title product 95 as a clear, colourless oil (2.75 g, 88%). Analytical data consistent with the literature (Halazy, S. et al., WO 9612713, Pierre Fabre Medicament (1996)). The volatiles were removed under high vacuum, THF (130 ml) was added the mixture was cooled to 0° C The reaction mixture was stirred for 1 h at 0° C. before being quenched by the addition of saturated aq. NH4Cl (100 ml) The reaction mixture was extracted with Et2O (4×75 ml) the combined organic phases were washed with brine (100 ml) before being dried (MgSO4) filtered concentrated to give the crude material This was purified by flash chromatography eluting with petrol/EtOAc (4:6)

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dimethylformamide (116 μL, 1.5 mmol, 0.1 eq.) and thionyl chloride (1.63 ml, 22.5 mmol, 1.5 eq.) were added to a solution of 5-bromovaleric acid (2.71 g, 15 mmol, 1 eq.) in toluene (20 ml) and the reaction mixture was stirred at 50° C. for 4 h. The volatiles were removed under high vacuum, THF (130 ml) was added and the mixture was cooled to 0° C. N,N-Diisopropylethylamine (4.2 ml, 24 mmol, 1.6 eq.) and ethylamine (2 M solution in THF, 9.0 ml, 18 mmol, 1.2 eq.) were added dropwise. The reaction mixture was stirred for 1 h at 0° C. before being quenched by the addition of saturated aq. NH4Cl (100 ml). The reaction mixture was extracted with Et2O (4×75 ml) and the combined organic phases were washed with brine (100 ml) before being dried (MgSO4), filtered, and concentrated to give the crude material. This was purified by flash chromatography, eluting with petrol/EtOAc (4:6), giving the title product 95 as a clear, colourless oil (2.75 g, 88%). Analytical data consistent with the literature (Halazy, S. et al., WO 9612713, Pierre Fabre Medicament (1996)). The volatiles were removed under high vacuum, THF (130 ml) was added the mixture was cooled to 0° C The reaction mixture was stirred for 1 h at 0° C. before being quenched by the addition of saturated aq. NH4Cl (100 ml) The reaction mixture was extracted with Et2O (4×75 ml) the combined organic phases were washed with brine (100 ml) before being dried (MgSO4) filtered concentrated to give the crude material This was purified by flash chromatography eluting with petrol/EtOAc (4:6)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Triphenylphosphine (2.88 g, 11 mmol, 1.1 eq.) was added to a solution of 5-bromo-N-ethylpentanamide 95 (2.08 g, 10 mmol, 1 eq.) in MeCN (5 ml) and the mixture was stirred for 14 h at 80° C. The mixture was allowed to cool to r.t. and concentrated under vacuum. The residue was added dropwise into Et2O (100 ml) and stirred vigorously for 10 min. The resulting solid was filtered, washed with Et2O (2×10 ml) and dissolved in CH2Cl2 (15 ml). This solution was then added dropwise into Et2O (200 ml) and stirred for 10 min. Solids were filtered, washed with Et2O (2×10 ml) and dried under high vacuum to give the title product 96 as a white powder (3.87 g, 82%). to cool to r.t. concentrated under vacuum The residue was added dropwise into Et2O (100 ml) stirred vigorously for 10 min The resulting solid was filtered washed with Et2O (2×10 ml) dissolved in CH2Cl2 (15 ml) This solution was then added dropwise into Et2O (200 ml) stirred for 10 min Solids were filtered washed with Et2O (2×10 ml) dried under high vacuum

反応条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Dimethylformamide (116 μL, 1.5 mmol, 0.1 eq.) and thionyl chloride (1.63 ml, 22.5 mmol, 1.5 eq.) were added to a solution of 5-bromovaleric acid (2.71 g, 15 mmol, 1 eq.) in toluene (20 ml) and the reaction mixture was stirred at 50° C. for 4 h. The volatiles were removed under high vacuum, THF (130 ml) was added and the mixture was cooled to 0° C. N,N-Diisopropylethylamine (4.2 ml, 24 mmol, 1.6 eq.) and ethylamine (2 M solution in THF, 9.0 ml, 18 mmol, 1.2 eq.) were added dropwise. The reaction mixture was stirred for 1 h at 0° C. before being quenched by the addition of saturated aq. NH4Cl (100 ml). The reaction mixture was extracted with Et2O (4×75 ml) and the combined organic phases were washed with brine (100 ml) before being dried (MgSO4), filtered, and concentrated to give the crude material. This was purified by flash chromatography, eluting with petrol/EtOAc (4:6), giving the title product 95 as a clear, colourless oil (2.75 g, 88%). Analytical data consistent with the literature (Halazy, S. et al., WO 9612713, Pierre Fabre Medicament (1996)). The volatiles were removed under high vacuum, THF (130 ml) was added the mixture was cooled to 0° C The reaction mixture was stirred for 1 h at 0° C. before being quenched by the addition of saturated aq. NH4Cl (100 ml) The reaction mixture was extracted with Et2O (4×75 ml) the combined organic phases were washed with brine (100 ml) before being dried (MgSO4) filtered concentrated to give the crude material This was purified by flash chromatography eluting with petrol/EtOAc (4:6)