2,2-Dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[1,3]dioxane-4,6-dione

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2-Dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[1,3]dioxane-4,6-dione 1b (15.72 g, 49.6 mmol) was dissolved in 280 mL of ethanol under stirring, then the reaction mixture was heated to 70° C. in an oil bath overnight. After cooling, the mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 3-oxo-4-(2,4,5-trifluoro-phenyl)-butyric acid ethyl ester 1c (12 g, yield 88%) as a yellow oil. After cooling the mixture was concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography

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

実験手順: 2,2-Dimethyl-[1,3]dioxane-4,6-dione (5.69 g, 39.5 mmol) was dissolved in 400 mL of dichloromethane under stirring, followed by addition of (2,4,5-trifluorophenyl)-acetic acid 1a (7.15 g, 37.6 mmol) and 4-dimethylaminopyridine (7.35 g, 60.2 mmol) in an ice-water bath. Then a suspension of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (8.28 g, 43.2 mmol) in 250 mL of dichloromethane was added dropwise slowly. After stirring at room temperature for 36 hours, the reaction mixture was washed with the solution of 5% potassium bisulfate (250 mL×7) and saturated brine (250 mL×2), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain the title compound 2,2-dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[1,3]dioxane-4,6-dione 1b (11.4 g, yield 96%) as a white solid. was added dropwise slowly After stirring at room temperature for 36 hours the reaction mixture was washed with the solution of 5% potassium bisulfate (250 mL×7) and saturated brine (250 mL×2) dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2-Dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[1,3]dioxane-4,6-dione 1b (15.72 g, 49.6 mmol) was dissolved in 280 mL of ethanol under stirring, then the reaction mixture was heated to 70° C. in an oil bath overnight. After cooling, the mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 3-oxo-4-(2,4,5-trifluoro-phenyl)-butyric acid ethyl ester 1c (12 g, yield 88%) as a yellow oil. After cooling the mixture was concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography

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

実験手順: 2,2-Dimethyl-[1,3]dioxane-4,6-dione (5.69 g, 39.5 mmol) was dissolved in 400 mL of dichloromethane under stirring, followed by addition of (2,4,5-trifluorophenyl)-acetic acid 1a (7.15 g, 37.6 mmol) and 4-dimethylaminopyridine (7.35 g, 60.2 mmol) in an ice-water bath. Then a suspension of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (8.28 g, 43.2 mmol) in 250 mL of dichloromethane was added dropwise slowly. After stirring at room temperature for 36 hours, the reaction mixture was washed with the solution of 5% potassium bisulfate (250 mL×7) and saturated brine (250 mL×2), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain the title compound 2,2-dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[1,3]dioxane-4,6-dione 1b (11.4 g, yield 96%) as a white solid. was added dropwise slowly After stirring at room temperature for 36 hours the reaction mixture was washed with the solution of 5% potassium bisulfate (250 mL×7) and saturated brine (250 mL×2) dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 114 g (0.60 mol) of 2,4,5-trifluorophenylacetic acid was dissolved in 600 mL of THF. To this mixture, 107 g (0.66 mol) of carbonyldiimidazole was added with stirring (when a part of carbonyldiimidazole was added, a lot of solid was formed; subsequently, the solid thereby dissolved in the solution with further addition). Upon completion of the addition, the reaction mixture was warmed to 50° C. 95.1 g (0.66 mol) of Meldrum's acid was added, and the mixture was aged for 3 hours at 50° C. The mixture was concentrated to remove THF and the residue was dissolved in water (600 mL) and dichloromethane (800 mL), and then the pH value was adjusted to 2. The aqueous phase was separated and the organic phase was washed with 0.1N HCl and water (600 mL) respectively. The organic phase was dried and concentrated to obtain 182 g of a condensate, 5-[2-(2,4,5-trifluorophenyl)-acetyl]-2,2-dimethyl-1,3-dioxane-4,6-dione, as a solid (the re-crystallization can be carried out in ethyl acetate to obtain a white solid). Melting point: 101.5-103.5° C., Yield: 96%. was added a lot of solid was formed subsequently, the solid thereby dissolved in the solution with further addition) Upon completion of the addition The mixture was concentrated to remove THF the residue was dissolved in water (600 mL) The aqueous phase was separated the organic phase was washed with 0.1N HCl and water (600 mL) respectively The organic phase was dried concentrated

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2-Dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[1,3]dioxane-4,6-dione 1b (15.72 g, 49.6 mmol) was dissolved in 280 mL of ethanol under stirring, then the reaction mixture was heated to 70° C. in an oil bath for 12 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography with system B as eluant to obtain the title compound ethyl 3-oxo-4-(2,4,5-trifluoro-phenyl)-butyrate 1c (12 g, yield 88%) as a yellow oil. MS m/z (ESI): 259 [M−1]. After cooling to room temperature the mixture was concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography with system B as eluant

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

実験手順: 2,2-Dimethyl-[1,3]dioxane-4,6-dione (5.69 g, 39.5 mmol) was dissolved in 400 mL of dichloromethane under stirring, followed by addition of 2,4,5-trifluorophenyl acetic acid 1a (7.15 g, 37.6 mmol) and 4-dimethylaminopyridine (7.35 g, 60.2 mmol) in an ice-water bath. Then a suspension of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (8.28 g, 43.2 mmol) in 250 mL of dichloromethane was added dropwise slowly. After stirring at room temperature for 36 hours, the reaction mixture was washed with the solution of 5% potassium bisulfate (250 mL×7) and saturated brine (250 mL×2), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain the title compound 2,2-dimethyl-5-[2-(2,4,5-trifluorophenyl)-acetyl]-[1,3]dioxane-4,6-dione 1b (11.4 g, yield 96%) as a white solid. MS m/z (ESI): 315.5 [M−1]. was added dropwise slowly After stirring at room temperature for 36 hours the reaction mixture was washed with the solution of 5% potassium bisulfate (250 mL×7) and saturated brine (250 mL×2) dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2-Dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[1,3]dioxane-4,6-dione 1b (15.72 g, 49.6 mmol) was dissolved in 280 mL of ethanol under stirring, then the reaction mixture was heated to 70° C. in an oil bath overnight. After cooling, the mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 3-oxo-4-(2,4,5-trifluoro-phenyl)-butyric acid ethyl ester 1c (12 g, yield 88%) as a yellow oil. After cooling the mixture was concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography

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

実験手順: 2,2-Dimethyl-[1,3]dioxane-4,6-dione (5.69 g, 39.5 mmol) was dissolved in 400 mL of dichloromethane under stirring, followed by addition of (2,4,5-trifluorophenyl)-acetic acid 1a (7.15 g, 37.6 mmol) and 4-dimethylaminopyridine (7.35 g, 60.2 mmol) in an ice-water bath. Then a suspension of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (8.28 g, 43.2 mmol) in 250 mL of dichloromethane was added dropwise slowly. After stirring at room temperature for 36 hours, the reaction mixture was washed with the solution of 5% potassium bisulfate (250 mL×7) and saturated brine (250 mL×2), dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain the title compound 2,2-dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[1,3]dioxane-4,6-dione 1b (11.4 g, yield 96%) as a white solid. was added dropwise slowly After stirring at room temperature for 36 hours the reaction mixture was washed with the solution of 5% potassium bisulfate (250 mL×7) and saturated brine (250 mL×2) dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2,2-Dimethyl-5-[2-(2,4,5-trifluoro-phenyl)-acetyl]-[1,3]dioxane-4,6-dione 1b (15.72 g, 49.6 mmol) was dissolved in 280 mL of ethanol under stirring, then the reaction mixture was heated to 70° C. in an oil bath overnight. After cooling, the mixture was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound 3-oxo-4-(2,4,5-trifluoro-phenyl)-butyric acid ethyl ester 1c (12 g, yield 88%) as a yellow oil. After cooling the mixture was concentrated under reduced pressure The resulting residue was purified by silica gel column chromatography