N-[4-(cyanomethyl)phenyl]acetamide

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

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

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Concentrated nitric acid (10 mL, >69% pure) was added to acetic anhydride (100 mL) cooled to −10° C. The solution was treated portionwise with N-[4-(cyanomethyl)phenyl]acetamide (5.0 g, 28.7 mmol) at a rate which maintained an internal temperature below −5° C. The solution was stirred for 1 hour while warming to room temperature. The solution was poured into an ice/water mixture and extracted several times with ethyl acetate. The combined extracts were washed with 10% Na2CO3 and brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate to provide 4.82 g (77%) of N-[4-(cyanomethyl)-2-nitrophenyl]acetamide. maintained an internal temperature below −5° C while warming to room temperature extracted several times with ethyl acetate The combined extracts were washed with 10% Na2CO3 and brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Concentrated nitric acid (10 mL, >69% pure) was added to acetic anhydride (100 mL) cooled to −10° C. The solution was treated portionwise with N-[4-(cyanomethyl)phenyl]acetamide (5.0 g, 28.7 mmol) at a rate which maintained an internal temperature below −5° C. The solution was stirred for 1 hour while warming to room temperature. The solution was poured into an ice/water mixture and extracted several times with ethyl acetate. The combined extracts were washed with 10% Na2CO3 and brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate to provide 4.82 g (77%) of N-[4-(cyanomethyl)-2-nitrophenyl]acetamide. maintained an internal temperature below −5° C while warming to room temperature extracted several times with ethyl acetate The combined extracts were washed with 10% Na2CO3 and brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Concentrated nitric acid (10 mL, >69% pure) was added to acetic anhydride (100 mL) cooled to −10° C. The solution was treated portionwise with N-[4-(cyanomethyl)phenyl]acetamide (5.0 g, 28.7 mmol) at a rate which maintained an internal temperature below −5° C. The solution was stirred for 1 hour while warming to room temperature. The solution was poured into an ice/water mixture and extracted several times with ethyl acetate. The combined extracts were washed with 10% Na2CO3 and brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate to provide 4.82 g (77%) of N-[4-(cyanomethyl)-2-nitrophenyl]acetamide. maintained an internal temperature below −5° C while warming to room temperature extracted several times with ethyl acetate The combined extracts were washed with 10% Na2CO3 and brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Concentrated nitric acid (10 mL, >69% pure) was added to acetic anhydride (100 mL) cooled to −10° C. The solution was treated portionwise with N-[4-(cyanomethyl)phenyl]acetamide (5.0 g, 28.7 mmol) at a rate which maintained an internal temperature below −5° C. The solution was stirred for 1 hour while warming to room temperature. The solution was poured into an ice/water mixture and extracted several times with ethyl acetate. The combined extracts were washed with 10% Na2CO3 and brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate to provide 4.82 g (77%) of N-[4-(cyanomethyl)-2-nitrophenyl]acetamide. maintained an internal temperature below −5° C while warming to room temperature extracted several times with ethyl acetate The combined extracts were washed with 10% Na2CO3 and brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Concentrated nitric acid (10 mL, >69% pure) was added to acetic anhydride (100 mL) cooled to −10° C. The solution was treated portionwise with N-[4-(cyanomethyl)phenyl]acetamide (5.0 g, 28.7 mmol) at a rate which maintained an internal temperature below −5° C. The solution was stirred for 1 hour while warming to room temperature. The solution was poured into an ice/water mixture and extracted several times with ethyl acetate. The combined extracts were washed with 10% Na2CO3 and brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate to provide 4.82 g (77%) of N-[4-(cyanomethyl)-2-nitrophenyl]acetamide. maintained an internal temperature below −5° C while warming to room temperature extracted several times with ethyl acetate The combined extracts were washed with 10% Na2CO3 and brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Concentrated nitric acid (10 mL, >69% pure) was added to acetic anhydride (100 mL) cooled to −10° C. The solution was treated portionwise with N-[4-(cyanomethyl)phenyl]acetamide (5.0 g, 28.7 mmol) at a rate which maintained an internal temperature below −5° C. The solution was stirred for 1 hour while warming to room temperature. The solution was poured into an ice/water mixture and extracted several times with ethyl acetate. The combined extracts were washed with 10% Na2CO3 and brine, dried (MgSO4), filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate to provide 4.82 g (77%) of N-[4-(cyanomethyl)-2-nitrophenyl]acetamide. maintained an internal temperature below −5° C while warming to room temperature extracted several times with ethyl acetate The combined extracts were washed with 10% Na2CO3 and brine dried (MgSO4) filtered concentrated under vacuum The residue was purified by flash column chromatography on silica gel with 1:1 hexanes/ethyl acetate

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 and ice-cooled solution of potassium tert-butoxide (0.432 g, 3.6566 mmol) in tert-butanol (15 ml), commercial 4-acetamidophenylacetonitrile (0.5096 g, 2.9252 mmol) and 1-azido-2-fluoro-4-trifluoromethyl-benzene (0.500 g, 2.4377 mmol) are added under a nitrogen atmosphere and the reaction mixture is allowed to attain spontaneously room temperature (1 h) and finally refluxed for 6 h. The resulting reaction mixture is concentrated, added water, and extracted with ethylacetate (3×100 ml). The combined organic layers are dried over MgSO4, filtered and evaporated, to afford a dark brown gummy material (0.900 g, 97% mass balance). The crude residue is purified by column chromatography over silica gel (230-400 mesh), eluting with 50% ethylacetate in petroleum ether, to obtain the title compound as a light yellow solid (0.270 g, 30% yield). M.p. 114.8-116.2° C. LC-ESI-HRMS of [M+H]+ shows 380.1125 Da. Calc. 380.113447 Da, dev. −2.5 ppm. are added under a nitrogen atmosphere to attain spontaneously room temperature (1 h) finally refluxed for 6 h The resulting reaction mixture is concentrated added water extracted with ethylacetate (3×100 ml) The combined organic layers are dried over MgSO4 filtered evaporated to afford a dark brown gummy material (0.900 g, 97% mass balance) The crude residue is purified by column chromatography over silica gel (230-400 mesh) eluting with 50% ethylacetate in petroleum ether

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

Procedure: To a cooled (0° C.) and stirred solution of 4-aminobenzyl cyanide (2.38 g, 18.04 mmol) in anhydrous dichloromethane (30 ml) was added anhydrous triethylamine (7.54 ml, 54.12 mmol) followed by acetic anhydride (2.56 ml, 27.06 mmol) under nitrogen. The mixture was allowed to warm to room temperature and it was stirred for 18 h before it was diluted with ethyl acetate (150 ml) and-washed with 10% aqueous sodium bicarbonate (100 ml), 2M hydrochloric acid (50 ml), brine (50 ml), then dried (MgSO4) and concentrated to give 4-(acetylamino)benzyl cyanide as an orange solid. The crude nitrile (2.8 g) was dissolved in absolute ethanol (200 ml) and chloroform (4 ml) and it was hydrogenated at 50 psi over platinum (IV) oxide for 16 h. The catalyst was filtered off, washed with ethanol and the filtrate was concentrated under vacuum. The residue was dissolved in 2M sodium hydroxide (30 ml) and the product was extracted with dichloromethane (4×150 ml), then dried (Na2SO4) and concentrated. Flash chromatography of the residue (silica gel, dichloromethane/methanol/ammonia, 85:15:1.5) gave 2.3 g (80%) of the title compound as a yellow solid. δ (360 MHz, CDCl3) 2.16 (3H, s), 2.71 (2H, t, J=6.8 Hz), 2.94 (2H, t, J=6.8 Hz), 7.14 (2H, d, J=8.3 Hz), 7.26 (1H, br s), 7.41 (2H, d, J=8.3 Hz). The catalyst was filtered off washed with ethanol the filtrate was concentrated under vacuum The residue was dissolved in 2M sodium hydroxide (30 ml) the product was extracted with dichloromethane (4×150 ml) dried (Na2SO4) concentrated

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a cooled (0° C.) and stirred solution of 4-aminobenzyl cyanide (2.38 g, 18.04 mmol) in anhydrous dichloromethane (30 ml) was added anhydrous triethylamine (7.54 ml, 54.12 mmol) followed by acetic anhydride (2.56 ml, 27.06 mmol) under nitrogen. The mixture was allowed to warm to room temperature and it was stirred for 18 h before it was diluted with ethyl acetate (150 ml) and-washed with 10% aqueous sodium bicarbonate (100 ml), 2M hydrochloric acid (50 ml), brine (50 ml), then dried (MgSO4) and concentrated to give 4-(acetylamino)benzyl cyanide as an orange solid. The crude nitrile (2.8 g) was dissolved in absolute ethanol (200 ml) and chloroform (4 ml) and it was hydrogenated at 50 psi over platinum (IV) oxide for 16 h. The catalyst was filtered off, washed with ethanol and the filtrate was concentrated under vacuum. The residue was dissolved in 2M sodium hydroxide (30 ml) and the product was extracted with dichloromethane (4×150 ml), then dried (Na2SO4) and concentrated. Flash chromatography of the residue (silica gel, dichloromethane/methanol/ammonia, 85:15:1.5) gave 2.3 g (80%) of the title compound as a yellow solid. δ (360 MHz, CDCl3) 2.16 (3H, s), 2.71 (2H, t, J=6.8 Hz), 2.94 (2H, t, J=6.8 Hz), 7.14 (2H, d, J=8.3 Hz), 7.26 (1H, br s), 7.41 (2H, d, J=8.3 Hz). to warm to room temperature -washed with 10% aqueous sodium bicarbonate (100 ml), 2M hydrochloric acid (50 ml), brine (50 ml) dried (MgSO4) concentrated