1,1,1-trifluoro-4-phenylbutan-2-one

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-bromobenzoic acid (2.53 g, 11.7 mmol), 1,1,1-trifluoro-4-phenylbutan-2-one (2.83 g, 14.0 mmol, see reference Yang, D; Wong, M; Yan, Z. J. Org. Chem. 2000, 65, 4179-4184), and Eaton's reagent (8.8 mL) in a sealed pressure tube was heated at 100° C. for 4 hours. The mixture was then cooled down to room temperature, ice-water was added slowly, and the mixture was stirred vigorously for about 15 minutes. The precipitated solid was filtered, washed with water, and air dried over night to afford the title compound as a light brown solid. The mixture was then cooled down to room temperature The precipitated solid was filtered washed with water, and air dried over night

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-bromobenzoic acid (2.53 g, 11.7 mmol), 1,1,1-trifluoro-4-phenylbutan-2-one (2.83 g, 14.0 mmol, see reference Yang, D; Wong, M; Yan, Z. J. Org. Chem. 2000, 65, 4179-4184), and Eaton's reagent (8.8 mL) in a sealed pressure tube was heated at 100° C. for 4 hours. The mixture was then cooled down to room temperature, ice-water was added slowly, and the mixture was stirred vigorously for about 15 minutes. The precipitated solid was filtered, washed with water, and air dried over night to afford the title compound as a light brown solid. The mixture was then cooled down to room temperature The precipitated solid was filtered washed with water, and air dried over night

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-iodobenzoic acid (5.73 g, 21.8 mmol), 1,1,1-trifluoro-4-phenylbutan-2-one (5.30 g, 26.2 mmol, see reference Yang, D; Wong, M; Yan, Z. J. Org. Chem. 2000, 65, 4179-4184), and Eaton's reagent (16 mL) in a sealed pressure tube was heated at 100° C. for 1.5 hours. The reaction was then cooled to room temperature and ice-water and DCM were added. Then the pH was adjusted to pH 9 by the slow addition of 50% aqueous NaOH and concentrated NH4OH solutions (the mixture was periodically cooled in an ice-water bath to maintain the temperature below 40° C.). The precipitated solid was filtered, washed with water and Et2O, and air dried to provide the title compound as the crude product. The reaction was then cooled to room temperature was periodically cooled in an ice-water bath to maintain the temperature below 40° C.) The precipitated solid was filtered washed with water and Et2O, and air dried

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-iodobenzoic acid (5.73 g, 21.8 mmol), 1,1,1-trifluoro-4-phenylbutan-2-one (5.30 g, 26.2 mmol, see reference Yang, D; Wong, M; Yan, Z. J. Org. Chem. 2000, 65, 4179-4184), and Eaton's reagent (16 mL) in a sealed pressure tube was heated at 100° C. for 1.5 hours. The reaction was then cooled to room temperature and ice-water and DCM were added. Then the pH was adjusted to pH 9 by the slow addition of 50% aqueous NaOH and concentrated NH4OH solutions (the mixture was periodically cooled in an ice-water bath to maintain the temperature below 40° C.). The precipitated solid was filtered, washed with water and Et2O, and air dried to provide the title compound as the crude product. The reaction was then cooled to room temperature was periodically cooled in an ice-water bath to maintain the temperature below 40° C.) The precipitated solid was filtered washed with water and Et2O, and air dried

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

実験手順: 200 mg (3.1 mmol) of potassium cyanide in 2 ml of water is added to 0.55 g (2.7 mmol) of 1,1,1-trifluoro-4-phenyl-butan-2-one (D. Yang; M-K. Wong; Z. Yan J. Org. Chem. (2000); 65; 4179-4184) in 4 ml of THF and 2 ml of water. It is cooled to 0° C., and 1 ml of a 25% sulfuric acid is added, allowed to heat to room temperature and stirred for 16 hours. Saturated sodium bicarbonate solution is added and extracted with ethyl acetate. After washing with saturated sodium chloride solution and drying on sodium sulfate, the crude cyanide, which is dissolved in 15 ml of diethyl ether and cooled to −70° C., is obtained quantitatively. 4.6 ml (5.5 mmol) of a 1.2 M DIBAL solution in toluene is added in drops over 10 minutes. It is allowed to heat for 2 hours to room temperature, quenched with 10% tartaric acid solution, and vigorous stirring is continued. After extraction with ethyl acetate, 5 g of silica gel and 10 ml of a 1 M sulfuric acid are added. It is stirred vigorously for 12 hours and filtered through Celite. The phases are separated, and it is extracted again with ethyl acetate. After chromatography on silica gel (hexane/ethyl acetate 30%), 300 mg of still contaminated 2-hydroxy-4-phenyl-2-(trifluoromethyl)-butanal is obtained. to heat to room temperature extracted with ethyl acetate After washing with saturated sodium chloride solution drying on sodium sulfate the crude cyanide, which is dissolved in 15 ml of diethyl ether cooled to −70° C. is obtained quantitatively to heat for 2 hours to room temperature quenched with 10% tartaric acid solution vigorous stirring After extraction with ethyl acetate, 5 g of silica gel and 10 ml of a 1 M sulfuric acid are added It is stirred vigorously for 12 hours filtered through Celite The phases are separated it is extracted again with ethyl acetate

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

実験手順: 200 mg (3.1 mmol) of potassium cyanide in 2 ml of water is added to 0.55 g (2.7 mmol) of 1,1,1-trifluoro-4-phenyl-butan-2-one (D. Yang; M -K. Wong; Z. Yan J. Org. Chem. (2000); 65; 4179-4184) in 4 mil of THF and 2 ml of water. It is cooled to 0° C., and 1 ml of a 25% sulfuric acid is added, allowed to heat to room temperature and stirred for 16 hours. Saturated sodium bicarbonate solution is added and extracted with ethyl acetate. After washing with saturated sodium chloride solution and drying on sodium sulfate, the crude cyanide, which is dissolved in 15 ml of diethyl ether and cooled to −70° C., is obtained quantitatively. 4.6 ml (5.5 mmol) of a 1.2 M DIBAL solution in toluene is added in drops over 10 minutes. It is allowed to heat for 2 hours to room temperature, quenched with 10% tartaric acid solution, and vigorous stirring is continued. After extraction with ethyl acetate, 5 g of silica gel and 10 ml of a 1 M sulfuric acid are added. It is stirred vigorously for 12 hours and filtered through Celite. The phases are separated, and it is extracted again with ethyl acetate. After chromatography on silica gel (hexane/ethyl acetate 30%), 300 mg of still contaminated 2-hydroxy-4-phenyl-2-(trifluoromethyl)-butanal is obtained. 0.5 ml (2.4 mmol) of titanium tetraethylate is added to the thus obtained aldehyde and 200 mg (1.13 mmol) of 5-amino-8-fluoro-2-methylquinazoline in 15 ml of toluene, and the mixture is heated for 2 hours to 100° C. After the cooling, it is poured into water, and vigorous stirring is continued. The suspension is filtered through Celite and thoroughly rewashed with ethyl acetate. The phases of the filtrate are separated, and it is extracted again with ethyl acetate. It is dried on sodium sulfate, and the solvent is removed in a vacuum. After chromatography on silica gel (hexane/ethyl acetate 30%), 100 mg of 1-(8-fluoro-2-methylquinazolin-5-ylimino)-4-phenyl-2-(trifluoromethyl)butan-2-ol is obtained. The imine is taken up in 5 ml of dichloromethane and cooled to −70° C. 1 ml (1 mmol) of a 1 M titanium tetrachloride solution in dichloromethane is added in drops over 10 minutes and stirred for one hour. The solution is poured into saturated sodium bicarbonate solution and stirred vigorously for 15 minutes. It is extracted with ethyl acetate, washed with. saturated sodium chloride solution, and dried on sodium sulfate. After concentration by evaporation and chromatography-on silica gel (hexane/ethyl acetate 50%), 44 mg of the desired product is obtained. to heat to room temperature extracted with ethyl acetate After washing with saturated sodium chloride solution drying on sodium sulfate the crude cyanide, which is dissolved in 15 ml of diethyl ether cooled to −70° C. is obtained quantitatively to heat for 2 hours to room temperature quenched with 10% tartaric acid solution vigorous stirring After extraction with ethyl acetate, 5 g of silica gel and 10 ml of a 1 M sulfuric acid are added It is stirred vigorously for 12 hours filtered through Celite The phases are separated it is extracted again with ethyl acetate

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

実験手順: 200 mg (3.1 mmol) of potassium cyanide in 2 ml of water is added to 0.55 g (2.7 mmol) of 1,1,1-trifluoro-4-phenyl-butan-2-one (D. Yang; M.-K. Wong; Z. Yan J. Org. Chem. (2000); 65; 4179-4184) in 4 ml of THF and 2 ml of water. It is cooled to 0° C., and 1 ml of a 25% sulfuric acid is added, allowed to heat to room temperature and stirred for 16 hours. Saturated sodium bicarbonate solution is added and extracted with ethyl acetate. After washing with saturated sodium chloride solution and drying on sodium sulfate, the crude cyanide, which is dissolved in 15 ml of diethyl ether and cooled to −70° C., is obtained quantitatively. 4.6 ml (5.5 mmol) of a 1.2 M DIBAL solution in toluene is added in drops over 10 minutes. It is allowed to heat for 2 hours to room temperature, quenched with 10% tartaric acid solution, and vigorous stirring is continued. After extraction with ethyl acetate, 5 g of silica gel and 10 ml of a 1 M sulfuric acid are added. It is stirred vigorously for 12 hours and filtered through Celite. The phases are separated, and it is extracted again with ethyl acetate. After chromatography on silica gel (hexane/ethyl acetate 30%), 300 mg of still contaminated 2-hydroxy-4-phenyl-2-(trifluoromethyl)-butanal is obtained. to heat to room temperature extracted with ethyl acetate After washing with saturated sodium chloride solution drying on sodium sulfate the crude cyanide, which is dissolved in 15 ml of diethyl ether cooled to −70° C. is obtained quantitatively to heat for 2 hours to room temperature quenched with 10% tartaric acid solution vigorous stirring After extraction with ethyl acetate, 5 g of silica gel and 10 ml of a 1 M sulfuric acid are added It is stirred vigorously for 12 hours filtered through Celite The phases are separated it is extracted again with ethyl acetate

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-bromobenzoic acid (2.53 g, 11.7 mmol), 1,1,1-trifluoro-4-phenylbutan-2-one (2.83 g, 14.0 mmol, see reference Yang, D; Wong, M; Yan, Z. J. Org. Chem. 2000, 65, 4179-4184), and Eaton's reagent (8.8 mL) in a sealed pressure tube was heated at 100° C. for 4 hours. The mixture was then cooled down to room temperature, ice-water was added slowly, and the mixture was stirred vigorously for about 15 minutes. The precipitated solid was filtered, washed with water, and air dried over night to afford the title compound as a light brown solid. The mixture was then cooled down to room temperature The precipitated solid was filtered washed with water, and air dried over night

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-iodobenzoic acid (5.73 g, 21.8 mmol), 1,1,1-trifluoro-4-phenylbutan-2-one (5.30 g, 26.2 mmol, see reference Yang, D; Wong, M; Yan, Z. J. Org. Chem. 2000, 65, 4179-4184), and Eaton's reagent (16 mL) in a sealed pressure tube was heated at 100° C. for 1.5 hours. The reaction was then cooled to room temperature and ice-water and DCM were added. Then the pH was adjusted to pH 9 by the slow addition of 50% aqueous NaOH and concentrated NH4OH solutions (the mixture was periodically cooled in an ice-water bath to maintain the temperature below 40° C.). The precipitated solid was filtered, washed with water and Et2O, and air dried to provide the title compound as the crude product. The reaction was then cooled to room temperature was periodically cooled in an ice-water bath to maintain the temperature below 40° C.) The precipitated solid was filtered washed with water and Et2O, and air dried