3-OXO-4-PHENYLBUTYRONITRILE

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under Ar(g), a solution of anhydrous acetonitrile (1.6 mL) in 35 mL anhydrous THF is cooled to −78° C. in a dry ice-acetone bath and then slowly treated with 12.2 mL of a 2.5 M n-butyl lithium in hexanes. The reaction mixture is maintained at −78° C. for an additional 45 min. and then slowly treated with a solution of 5 gms. of phenyl-acetic acid ethyl ester in 5 mL of anhydrous THF. The resulting solution is then stirred overnight at room temperature. Subsequently, the reaction mixture is treated with 10% NaOH(aq) to dissolve solids and then extracted with ethyl acetate. The aqueous layer is acidified (pH 6) with HCl(aq) affording a white precipitate which subsequently is filtered. The organic layer is concentrated in vacuo, and the residue is triturated with isopropanol resulting in the formation of additional white precipitate. The combined precipitates provide the desired 3-oxo-4-phenyl-butyronitrile in the amount of 4.0262 gms. slowly treated with a solution of 5 gms to dissolve solids extracted with ethyl acetate affording a white precipitate which subsequently is filtered The organic layer is concentrated in vacuo the residue is triturated with isopropanol resulting in the formation of additional white precipitate The combined precipitates

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under Ar(g), a solution of anhydrous acetonitrile (1.6 mL) in 35 mL anhydrous THF is cooled to −78° C. in a dry ice-acetone bath and then slowly treated with 12.2 mL of a 2.5 M n-butyl lithium in hexanes. The reaction mixture is maintained at −78° C. for an additional 45 min. and then slowly treated with a solution of 5 gms. of phenyl-acetic acid ethyl ester in 5 mL of anhydrous THF. The resulting solution is then stirred overnight at room temperature. Subsequently, the reaction mixture is treated with 10% NaOH(aq) to dissolve solids and then extracted with ethyl acetate. The aqueous layer is acidified (pH 6) with HCl(aq) affording a white precipitate which subsequently is filtered. The organic layer is concentrated in vacuo, and the residue is triturated with isopropanol resulting in the formation of additional white precipitate. The combined precipitates provide the desired 3-oxo-4-phenyl-butyronitrile in the amount of 4.0262 gms. slowly treated with a solution of 5 gms to dissolve solids extracted with ethyl acetate affording a white precipitate which subsequently is filtered The organic layer is concentrated in vacuo the residue is triturated with isopropanol resulting in the formation of additional white precipitate The combined precipitates

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under Ar(g), a solution of anhydrous acetonitrile (1.6 mL) in 35 mL anhydrous THF is cooled to −78° C. in a dry ice-acetone bath and then slowly treated with 12.2 mL of a 2.5 M n-butyl lithium in hexanes. The reaction mixture is maintained at −78° C. for an additional 45 min. and then slowly treated with a solution of 5 gms. of phenyl-acetic acid ethyl ester in 5 mL of anhydrous THF. The resulting solution is then stirred overnight at room temperature. Subsequently, the reaction mixture is treated with 10% NaOH(aq) to dissolve solids and then extracted with ethyl acetate. The aqueous layer is acidified (pH 6) with HCl(aq) affording a white precipitate which subsequently is filtered. The organic layer is concentrated in vacuo, and the residue is triturated with isopropanol resulting in the formation of additional white precipitate. The combined precipitates provide the desired 3-oxo-4-phenyl-butyronitrile in the amount of 4.0262 gms. slowly treated with a solution of 5 gms to dissolve solids extracted with ethyl acetate affording a white precipitate which subsequently is filtered The organic layer is concentrated in vacuo the residue is triturated with isopropanol resulting in the formation of additional white precipitate The combined precipitates

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under Ar(g), a solution of anhydrous acetonitrile (1.6 mL) in 35 mL anhydrous THF is cooled to −78° C. in a dry ice-acetone bath and then slowly treated with 12.2 mL of a 2.5 M n-butyl lithium in hexanes. The reaction mixture is maintained at −78° C. for an additional 45 min. and then slowly treated with a solution of 5 gms. of phenyl-acetic acid ethyl ester in 5 mL of anhydrous THF. The resulting solution is then stirred overnight at room temperature. Subsequently, the reaction mixture is treated with 10% NaOH(aq) to dissolve solids and then extracted with ethyl acetate. The aqueous layer is acidified (pH 6) with HCl(aq) affording a white precipitate which subsequently is filtered. The organic layer is concentrated in vacuo, and the residue is triturated with isopropanol resulting in the formation of additional white precipitate. The combined precipitates provide the desired 3-oxo-4-phenyl-butyronitrile in the amount of 4.0262 gms. slowly treated with a solution of 5 gms to dissolve solids extracted with ethyl acetate affording a white precipitate which subsequently is filtered The organic layer is concentrated in vacuo the residue is triturated with isopropanol resulting in the formation of additional white precipitate The combined precipitates

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under Ar(g), a solution of anhydrous acetonitrile (1.6 mL) in 35 mL anhydrous THF is cooled to −78° C. in a dry ice-acetone bath and then slowly treated with 12.2 mL of a 2.5 M n-butyl lithium in hexanes. The reaction mixture is maintained at −78° C. for an additional 45 min. and then slowly treated with a solution of 5 gms. of phenyl-acetic acid ethyl ester in 5 mL of anhydrous THF. The resulting solution is then stirred overnight at room temperature. Subsequently, the reaction mixture is treated with 10% NaOH(aq) to dissolve solids and then extracted with ethyl acetate. The aqueous layer is acidified (pH 6) with HCl(aq) affording a white precipitate which subsequently is filtered. The organic layer is concentrated in vacuo, and the residue is triturated with isopropanol resulting in the formation of additional white precipitate. The combined precipitates provide the desired 3-oxo-4-phenyl-butyronitrile in the amount of 4.0262 gms. slowly treated with a solution of 5 gms to dissolve solids extracted with ethyl acetate affording a white precipitate which subsequently is filtered The organic layer is concentrated in vacuo the residue is triturated with isopropanol resulting in the formation of additional white precipitate The combined precipitates

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under Ar(g), a solution of anhydrous acetonitrile (1.6 mL) in 35 mL anhydrous THF is cooled to −78° C. in a dry ice-acetone bath and then slowly treated with 12.2 mL of a 2.5 M n-butyl lithium in hexanes. The reaction mixture is maintained at −78° C. for an additional 45 min. and then slowly treated with a solution of 5 gms. of phenyl-acetic acid ethyl ester in 5 mL of anhydrous THF. The resulting solution is then stirred overnight at room temperature. Subsequently, the reaction mixture is treated with 10% NaOH(aq) to dissolve solids and then extracted with ethyl acetate. The aqueous layer is acidified (pH 6) with HCl(aq) affording a white precipitate which subsequently is filtered. The organic layer is concentrated in vacuo, and the residue is triturated with isopropanol resulting in the formation of additional white precipitate. The combined precipitates provide the desired 3-oxo-4-phenyl-butyronitrile in the amount of 4.0262 gms. slowly treated with a solution of 5 gms to dissolve solids extracted with ethyl acetate affording a white precipitate which subsequently is filtered The organic layer is concentrated in vacuo the residue is triturated with isopropanol resulting in the formation of additional white precipitate The combined precipitates

反应条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Under Ar(g), a solution of anhydrous acetonitrile (1.6 mL) in 35 mL anhydrous THF is cooled to −78° C. in a dry ice-acetone bath and then slowly treated with 12.2 mL of a 2.5 M n-butyl lithium in hexanes. The reaction mixture is maintained at −78° C. for an additional 45 min. and then slowly treated with a solution of 5 gms. of phenyl-acetic acid ethyl ester in 5 mL of anhydrous THF. The resulting solution is then stirred overnight at room temperature. Subsequently, the reaction mixture is treated with 10% NaOH(aq) to dissolve solids and then extracted with ethyl acetate. The aqueous layer is acidified (pH 6) with HCl(aq) affording a white precipitate which subsequently is filtered. The organic layer is concentrated in vacuo, and the residue is triturated with isopropanol resulting in the formation of additional white precipitate. The combined precipitates provide the desired 3-oxo-4-phenyl-butyronitrile in the amount of 4.0262 gms. slowly treated with a solution of 5 gms to dissolve solids extracted with ethyl acetate affording a white precipitate which subsequently is filtered The organic layer is concentrated in vacuo the residue is triturated with isopropanol resulting in the formation of additional white precipitate The combined precipitates

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of cyanoacetic acid (2 g, 23.5 mmol) in THF (100 mL) at −78° C. was added nBuLi (10 mL, 25.9 mmol, 2.5M in hexanes). After 30 min, phenylacetyl chloride (1.6 mL, 11.8 mmol) was added dropwise. Following an additional 30 min, the solution was partitioned between 1N HCl-Et2O and the aqueous phase was washed several times with Et2O. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (silica, 30% EtOAc in hexanes) yielding the title compound (770 mg, 40%) as a tan oil: LCMS (ES) m/z 160 (M+H)+. Following an additional 30 min the solution was partitioned between 1N HCl-Et2O the aqueous phase was washed several times with Et2O The combined organic fractions were dried over Na2SO4 concentrated purified via column chromatography (silica, 30% EtOAc in hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of cyanoacetic acid (2 g, 23.5 mmol) in THF (100 mL) at −78° C. was added nBuLi (10 mL, 25.9 mmol, 2.5M in hexanes). After 30 min, phenylacetyl chloride (1.6 mL, 11.8 mmol) was added dropwise. Following an additional 30 min, the solution was partitioned between 1N HCl-Et2O and the aqueous phase was washed several times with Et2O. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (silica, 30% EtOAc in hexanes) yielding the title compound (770 mg, 40%) as a tan oil: LCMS (ES) m/z 160 (M+H)+. Following an additional 30 min the solution was partitioned between 1N HCl-Et2O the aqueous phase was washed several times with Et2O The combined organic fractions were dried over Na2SO4 concentrated purified via column chromatography (silica, 30% EtOAc in hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of cyanoacetic acid (2 g, 23.5 mmol) in THF (100 mL) at −78° C. was added nBuLi (10 mL, 25.9 mmol, 2.5M in hexanes). After 30 min, phenylacetyl chloride (1.6 mL, 11.8 mmol) was added dropwise. Following an additional 30 min, the solution was partitioned between 1N HCl-Et2O and the aqueous phase was washed several times with Et2O. The combined organic fractions were dried over Na2SO4, concentrated and purified via column chromatography (silica, 30% EtOAc in hexanes) yielding the title compound (770 mg, 40%) as a tan oil: LCMS (ES) m/z 160 (M+H)+. Following an additional 30 min the solution was partitioned between 1N HCl-Et2O the aqueous phase was washed several times with Et2O The combined organic fractions were dried over Na2SO4 concentrated purified via column chromatography (silica, 30% EtOAc in hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-oxo-4-phenylbutanenitrile (690 mg, 4.34 mmol) in ethanol (25 mL) is added pyridine (4.91 mL, 60.7 mmol) and hydroxylamine hydrochloride (301 mg, 4.34 mmol). The reaction mixture is allowed to stir at room temperature 84 h. The mixture is diluted with ethyl acetate and 1M aqueous NaOH solution. The layers are separated and the aqueous layer is extracted with ethyl acetate. The organic layers are washed with brine, dried (Na2SO4), and the solvent is removed in vacuo to afford the title compound as a yellow solid (702 mg, 93%). LCMS: 175.20 (M+H+). The layers are separated the aqueous layer is extracted with ethyl acetate The organic layers are washed with brine dried (Na2SO4) the solvent is removed in vacuo

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of 60% sodium hydride in mineral oil (1.00 g, 25.0 mmol) in THF (40 mL) at reflux is added a solution of methyl phenylacetate (2.50 g, 16.6 mmol) and anhydrous acetonitrile (1.74 mL, 33.3 mmol) in THF (40 mL), dropwise. The mixture is stirred at reflux for 6 h, then cooled to room temperature and stirred an additional 16 h. The reaction is quenched with H2O and is stirred for 10 min, after which the mixture is diluted with ethyl acetate and saturated aqueous NaHCO3 solution. The layers are separated and the aqueous layer is extracted with ethyl acetate. The organic layers are washed with brine and dried (Na2SO4). The solvent is removed in vacuo and the crude material is purified via flash column chromatography using a gradient elution of 0-40% ethyl acetate/heptane to afford the title compound as a yellow oil (690 mg, 26%). LCMS: 160.20 (M+H+). at reflux at reflux for 6 h stirred an additional 16 h The reaction is quenched with H2O is stirred for 10 min after which the mixture is diluted with ethyl acetate and saturated aqueous NaHCO3 solution The layers are separated the aqueous layer is extracted with ethyl acetate The organic layers are washed with brine dried (Na2SO4) The solvent is removed in vacuo the crude material is purified via flash column chromatography a gradient elution of 0-40% ethyl acetate/heptane