西他列汀杂质66

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: 3-Oxo-4-(2,4,5-trifluoro-phenyl)-butyric acid ethyl ester 1c (24.6 g, 94.5 mmol) was dissolved in 240 mL of methanol, and ammonium acetate (36.4 g, 473 mmol) was added to the solution. The reaction mixture was heated to reflux for 3 hours and monitored by thin layer chromatography until the disappearance of the starting materials. The reaction mixture was concentrated under reduced pressure, and then 100 mL of water was added to the residue. The mixture was extracted with ethyl acetate (200 mL×3), and the combined organic phase was washed with 200 mL of saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a light yellow solid. The resulting solid was dissolved in 50 mL of ethyl acetate at 80° C., and then 50 mL of n-hexane and seed-crystal were added to the solution. The mixture was cooled to room temperature, and, half an hour later, 100 mL of n-hexane was added. The mixture was stored in refrigerator overnight and then filtered under reduced pressure to obtain the title compound 3-amino-4-(2,4,5-trifluoro-phenyl)-but-2-enoic acid ethyl ester 1d (19.5 g, yield 80%) as a white solid. The reaction mixture was heated to reflux for 3 hours The reaction mixture was concentrated under reduced pressure 100 mL of water was added to the residue The mixture was extracted with ethyl acetate (200 mL×3) the combined organic phase was washed with 200 mL of saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure to obtain a light yellow solid was stored in refrigerator overnight filtered under reduced pressure

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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

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

实验步骤: 3-Oxo-4-(2,4,5-trifluoro-phenyl)-butyric acid ethyl ester 1c (24.6 g, 94.5 mmol) was dissolved in 240 mL of methanol, and ammonium acetate (36.4 g, 473 mmol) was added to the solution. The reaction mixture was heated to reflux for 3 hours and monitored by thin layer chromatography until the disappearance of the starting materials. The reaction mixture was concentrated under reduced pressure, and then 100 mL of water was added to the residue. The mixture was extracted with ethyl acetate (200 mL×3), and the combined organic phase was washed with 200 mL of saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a light yellow solid. The resulting solid was dissolved in 50 mL of ethyl acetate at 80° C., and then 50 mL of n-hexane and seed-crystal were added to the solution. The mixture was cooled to room temperature, and, half an hour later, 100 mL of n-hexane was added. The mixture was stored in refrigerator overnight and then filtered under reduced pressure to obtain the title compound 3-amino-4-(2,4,5-trifluoro-phenyl)-but-2-enoic acid ethyl ester 1d (19.5 g, yield 80%) as a white solid. The reaction mixture was heated to reflux for 3 hours The reaction mixture was concentrated under reduced pressure 100 mL of water was added to the residue The mixture was extracted with ethyl acetate (200 mL×3) the combined organic phase was washed with 200 mL of saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure to obtain a light yellow solid was stored in refrigerator overnight filtered under reduced pressure

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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

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

实验步骤: Ethyl 3-oxo-4-(2,4,5-trifluoro-phenyl)-butyrate 1c (24.6 g, 94.5 mmol) was dissolved in 240 mL of methanol, and ammonium acetate (36.4 g, 473 mmol) was added to the solution. The reaction mixture was heated to reflux for 3 hours. The reaction mixture was concentrated under reduced pressure, and then 100 mL of water was added to the residues. The mixture was extracted with ethyl acetate (200 mL×3), and the combined organic phase was washed with 200 mL of saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a light yellow solid. The resulting solid was dissolved in 50 mL of ethyl acetate at 80° C., and then 50 mL of n-hexane and seed-crystal were added to the solution. The mixture was cooled to room temperature, and half an hour later, 100 mL of n-hexane was added. The mixture was stored in refrigerator for 12 hours and then filtered to obtain the title compound ethyl 3-amino-4-(2,4,5-trifluoro-phenyl)-but-2-enoate 1d (19.5 g, yield 80%) as a white solid. MS m/z (ESI): 260.1 [M+1]. The reaction mixture was heated to reflux for 3 hours The reaction mixture was concentrated under reduced pressure 100 mL of water was added to the residues The mixture was extracted with ethyl acetate (200 mL×3) the combined organic phase was washed with 200 mL of saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure to obtain a light yellow solid filtered

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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

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

实验步骤: 3-Oxo-4-(2,4,5-trifluoro-phenyl)-butyric acid ethyl ester 1c (24.6 g, 94.5 mmol) was dissolved in 240 mL of methanol, and ammonium acetate (36.4 g, 473 mmol) was added to the solution. The reaction mixture was heated to reflux for 3 hours and monitored by thin layer chromatography until the disappearance of the starting materials. The reaction mixture was concentrated under reduced pressure, and then 100 mL of water was added to the residue. The mixture was extracted with ethyl acetate (200 mL×3), and the combined organic phase was washed with 200 mL of saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a light yellow solid. The resulting solid was dissolved in 50 mL of ethyl acetate at 80° C., and then 50 mL of n-hexane and seed-crystal were added to the solution. The mixture was cooled to room temperature, and, half an hour later, 100 mL of n-hexane was added. The mixture was stored in refrigerator overnight and then filtered under reduced pressure to obtain the title compound 3-amino-4-(2,4,5-trifluoro-phenyl)-but-2-enoic acid ethyl ester 1d (19.5 g, yield 80%) as a white solid. The reaction mixture was heated to reflux for 3 hours The reaction mixture was concentrated under reduced pressure 100 mL of water was added to the residue The mixture was extracted with ethyl acetate (200 mL×3) the combined organic phase was washed with 200 mL of saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure to obtain a light yellow solid was stored in refrigerator overnight filtered under reduced pressure

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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

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

实验步骤: 3-Oxo-4-(2,4,5-trifluoro-phenyl)-butyric acid ethyl ester 1c (24.6 g, 94.5 mmol) was dissolved in 240 mL of methanol, and ammonium acetate (36.4 g, 473 mmol) was added to the solution. The reaction mixture was heated to reflux for 3 hours and monitored by thin layer chromatography until the disappearance of the starting materials. The reaction mixture was concentrated under reduced pressure, and then 100 mL of water was added to the residue. The mixture was extracted with ethyl acetate (200 mL×3), and the combined organic phase was washed with 200 mL of saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain a light yellow solid. The resulting solid was dissolved in 50 mL of ethyl acetate at 80° C., and then 50 mL of n-hexane and seed-crystal were added to the solution. The mixture was cooled to room temperature, and, half an hour later, 100 mL of n-hexane was added. The mixture was stored in refrigerator overnight and then filtered under reduced pressure to obtain the title compound 3-amino-4-(2,4,5-trifluoro-phenyl)-but-2-enoic acid ethyl ester 1d (19.5 g, yield 80%) as a white solid. The reaction mixture was heated to reflux for 3 hours The reaction mixture was concentrated under reduced pressure 100 mL of water was added to the residue The mixture was extracted with ethyl acetate (200 mL×3) the combined organic phase was washed with 200 mL of saturated brine dried over anhydrous magnesium sulfate filtered concentrated under reduced pressure to obtain a light yellow solid was stored in refrigerator overnight filtered under reduced pressure

反应条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 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