1-(2-aminophenyl)-2-methylpropan-1-one

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

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

Procedure: Dry hydrogen chloride gas is piped through a solution of 2.86 g of 1-(2-amino-phenyl)-2-methyl-propan-1-one and 1.33 ml of chloroacetonitrile in 14 ml dioxane with stirring at ambient temperature for approx. five hours. Then the dioxane is largely distilled off in a water jet vacuum. The honey-like residue is combined with ice water and the resulting suspension is made alkaline with saturated potassium carbonate solution while cooling with an ice bath. The precipitate is suction filtered, washed with water and dried. The crude product is purified by chromatography over a silica gel column with petroleum ether/methylene chloride (8:2 to 0:1) as eluant. Then the dioxane is largely distilled off in a water jet vacuum while cooling with an ice bath filtered washed with water dried The crude product is purified by chromatography over a silica gel column with petroleum ether/methylene chloride (8:2 to 0:1) as eluant

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

Procedure: Dry hydrogen chloride gas is piped through a solution of 2.86 g of 1-(2-amino-phenyl)-2-methyl-propan-1-one and 1.33 ml of chloroacetonitrile in 14 ml dioxane with stirring at ambient temperature for approx. five hours. Then the dioxane is largely distilled off in a water jet vacuum. The honey-like residue is combined with ice water and the resulting suspension is made alkaline with saturated potassium carbonate solution while cooling with an ice bath. The precipitate is suction filtered, washed with water and dried. The crude product is purified by chromatography over a silica gel column with petroleum ether/methylene chloride (8:2 to 0:1) as eluant. Then the dioxane is largely distilled off in a water jet vacuum while cooling with an ice bath filtered washed with water dried The crude product is purified by chromatography over a silica gel column with petroleum ether/methylene chloride (8:2 to 0:1) as eluant

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

Procedure: Dry hydrogen chloride gas is piped through a solution of 2.86 g of 1-(2-amino-phenyl)-2-methyl-propan-1-one and 1.33 ml of chloroacetonitrile in 14 ml dioxane with stirring at ambient temperature for approx. five hours. Then the dioxane is largely distilled off in a water jet vacuum. The honey-like residue is combined with ice water and the resulting suspension is made alkaline with saturated potassium carbonate solution while cooling with an ice bath. The precipitate is suction filtered, washed with water and dried. The crude product is purified by chromatography over a silica gel column with petroleum ether/methylene chloride (8:2 to 0:1) as eluant. Then the dioxane is largely distilled off in a water jet vacuum while cooling with an ice bath filtered washed with water dried The crude product is purified by chromatography over a silica gel column with petroleum ether/methylene chloride (8:2 to 0:1) as eluant

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

Procedure: A mixture of 1-(2-aminophenyl)-2-methyl-1-propanone (5.526 gm, 33.9 mmol), ethyl p-fluorobenzoylacetate (7.12 gm, 33.9 mmol) and concentrated H2SO4 (0.34 ml) in glacial HOAc (34 ml) was refluxed for 22 hours. The reaction mixture was cooled to room temperature and poured into an ice-cold solution of concentrated NH4OH (48 ml) in H2O (120 ml). The resulting mixture was extracted twice with Et2O and the combined Et2O layers were washed with H2O and brine, then dried (Na2SO4), filtered and stripped to yield a cloudy brown oil. Flash chromatography (Merck SiO2, 10% EtOAc in hexane) afforded impure 2-(4-fluorophenyl)-4-(1-methylethyl)-3-quinoline-carboxylic acid, ethyl ester as an oil. Most of the volatile impurities were distilled off under an oil pump vacuum (bath temp. 85° C.), leaving a yellow oil (5.096 gm) which was 77% by weight 2-(4-fluorophenyl)-4-(1-methylethyl)-3-quinolinecarboxylic acid, ethyl ester (34% effective yield). was refluxed for 22 hours The resulting mixture was extracted twice with Et2O the combined Et2O layers were washed with H2O and brine dried (Na2SO4) filtered to yield a cloudy brown oil

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

Procedure: A solution of anthranilonitrile (8.507 gm, 72 mmol) in dry Et2O (20 ml) was added to i-propylmagnesium chloride (2.0M in Et2O, 100 ml, 200 mmol) in dry Et2O (30 ml) at 0° C. over a 15 minute period. After the addition was complete, the mixture was warmed to room temperature and stirred for 4.5 hours. The solution was cooled to 0° C., quenched with 10% HCl (150 ml), then stirred for 25 minutes. The aqueous layer was made basic with solid NaOH (25 gm) and then extracted with Et2O (3×). The combined Et2O extracts were washed with brine, then dried (Na2SO4), filtered and stripped to give a yellow oil. Flash Chromatography of the oil (Merck SiO2, 15% EtOAc in hexane) afforded 1-(2-aminophenyl)-2-methyl-1-propanone (10.916 gm, 93%) as a golden yellow oil. After the addition The solution was cooled to 0° C. quenched with 10% HCl (150 ml) stirred for 25 minutes extracted with Et2O (3×) The combined Et2O extracts were washed with brine dried (Na2SO4) filtered to give a yellow oil

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

Procedure: A solution of anthranilonitrile (8.507 gm, 72 mmol) in dry Et2O (20 ml) was added to i-propylmagnesium chloride (2.0M in Et2O, 100 ml, 200 mmol) in dry Et2O (30 ml) at 0° C. over a 15 minute period. After the addition was complete, the mixture was warmed to room temperature and stirred for 4.5 hours. The solution was cooled to 0° C., quenched with 10% HCl (150 ml), then stirred for 25 minutes. The aqueous layer was made basic with solid NaOH (25 gm) and then extracted with Et2O (3×). The combined Et2O extracts were washed with brine, then dried (Na2SO4), filtered and stripped to give a yellow oil. Flash Chromatography of the oil (Merck SiO2, 15% EtOAc in hexane) afforded 1-(2-aminophenyl)-2-methyl-1-propanone (10.916 gm, 93%) as a golden yellow oil. After the addition The solution was cooled to 0° C. quenched with 10% HCl (150 ml) stirred for 25 minutes extracted with Et2O (3×) The combined Et2O extracts were washed with brine dried (Na2SO4) filtered to give a yellow oil

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

Procedure: A mixture of 1-(2-aminophenyl)-2-methyl-1-propanone (5.526 gm, 33.9 mmol), ethyl p-fluorobenzoylacetate (7.12 gm, 33.9 mmol) and concentrated H2SO4 (0.34 ml) in glacial HOAc (34 ml) was refluxed for 22 hours. The reaction mixture was cooled to room temperature and poured into an ice-cold solution of concentrated NH4OH (48 ml) in H2O (120 ml). The resulting mixture was extracted twice with Et2O and the combined Et2O layers were washed with H2O and brine, then dried (Na2SO2), filtered and stripped to yield a cloudy brown oil. Flash chromatography (Merck SiO2, 10% EtOAc in hexane) afforded impure 2-(4-fluorophenyl)-4-(1-methylethyl)-3-quinoline-carboxylic acid, ethyl ester as an oil. Most of the volatile impurities were distilled off under an oil pump vacuum (bath temp. 85° C.), leaving a yellow oil (5.096 gm) which was 77% by weight 2-(4-fluorophenyl)-4-(1-methylethyl)-3-quinolinecarboxylic acid, ethyl ester (34% effective yield). was refluxed for 22 hours The resulting mixture was extracted twice with Et2O the combined Et2O layers were washed with H2O and brine dried (Na2SO2) filtered to yield a cloudy brown oil

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

Procedure: A mixture of 1-(2-aminophenyl)-2-methyl-1-propanone (5.526 gm, 33.9 mmol), ethyl p-fluorobenzoylacetate (7.12 gm, 33.9 mmol) and concentrated H2SO4 (0.34 ml) in glacial HOAc (34 ml) was refluxed for 22 hours. The reaction mixture was cooled to room temperature and poured into an ice-cold solution of concentrated NH4OH (48 ml) in H2O (120 ml). The resulting mixture was extracted twice with Et2O and the combined Et2O layers were washed with H2O and brine, then dried (Na2SO2), filtered and stripped to yield a cloudy brown oil. Flash chromatography (Merck SiO2, 10% EtOAc in hexane) afforded impure 2-(4-fluorophenyl)-4-(1-methylethyl)-3-quinoline-carboxylic acid, ethyl ester as an oil. Most of the volatile impurities were distilled off under an oil pump vacuum (bath temp. 85° C.), leaving a yellow oil (5.096 gm) which was 77% by weight 2-(4-fluorophenyl)-4-(1-methylethyl)-3-quinolinecarboxylic acid, ethyl ester (34% effective yield). was refluxed for 22 hours The resulting mixture was extracted twice with Et2O the combined Et2O layers were washed with H2O and brine dried (Na2SO2) filtered to yield a cloudy brown oil

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

Procedure: A solution of anthranilonitrile (8.507 gm, 72 mmol) in dry Et2O (20 ml) was added to i-propylmagnesium chloride (2.0M in Et2O, 100 ml, 200 mmol) in dry Et2O (30 ml) at 0° C. over a 15 minute period. After the addition was complete, the mixture was warmed to room temperature and stirred for 4.5 hours. The solution was cooled to 0° C., quenched with 10% HCl (150 ml), then stirred for 25 minutes. The aqueous layer was made basic with solid NaOH (25 gm) and then extracted with Et2O (3×). The combined Et2O extracts were washed with brine, then dried (Na2SO4), filtered and stripped to give a yellow oil. Flash Chromatography of the oil (Merck SiO2, 15% EtOAc in hexane) afforded 1-(2-aminophenyl)-2-methyl-1-propanone (10.916 gm, 93%) as a golden yellow oil. After the addition The solution was cooled to 0° C. quenched with 10% HCl (150 ml) stirred for 25 minutes extracted with Et2O (3×) The combined Et2O extracts were washed with brine dried (Na2SO4) filtered to give a yellow oil

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

Procedure: Dry hydrogen chloride gas is piped through a solution of 2.86 g of 1-(2-amino-phenyl)-2-methyl-propan-1-one and 1.33 ml of chloroacetonitrile in 14 ml dioxane with stirring at ambient temperature for approx. five hours. Then the dioxane is largely distilled off in a water jet vacuum. The honey-like residue is combined with ice water and the resulting suspension is made alkaline with saturated potassium carbonate solution while cooling with an ice bath. The precipitate is suction filtered, washed with water and dried. The crude product is purified by chromatography over a silica gel column with petroleum ether/methylene chloride (8:2 to 0:1) as eluant. Then the dioxane is largely distilled off in a water jet vacuum while cooling with an ice bath filtered washed with water dried The crude product is purified by chromatography over a silica gel column with petroleum ether/methylene chloride (8:2 to 0:1) as eluant

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

Procedure: Dry hydrogen chloride gas is piped through a solution of 2.86 g of 1-(2-amino-phenyl)-2-methyl-propan-1-one and 1.33 ml of chloroacetonitrile in 14 ml dioxane with stirring at ambient temperature for approx. five hours. Then the dioxane is largely distilled off in a water jet vacuum. The honey-like residue is combined with ice water and the resulting suspension is made alkaline with saturated potassium carbonate solution while cooling with an ice bath. The precipitate is suction filtered, washed with water and dried. The crude product is purified by chromatography over a silica gel column with petroleum ether/methylene chloride (8:2 to 0:1) as eluant. Then the dioxane is largely distilled off in a water jet vacuum while cooling with an ice bath filtered washed with water dried The crude product is purified by chromatography over a silica gel column with petroleum ether/methylene chloride (8:2 to 0:1) as eluant