Hexane → 3-Amino-4-(2,4,5-trifluorophenyl)but-2-enoic acid ethyl ester

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.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux for 3 hours
3. concentrationThe reaction mixture was concentrated under reduced pressure
4. addition100 mL of water was added to the residue
5. extractionThe mixture was extracted with ethyl acetate (200 mL×3)
6. washthe combined organic phase was washed with 200 mL of saturated brine
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto obtain a light yellow solid
11. customwas stored in refrigerator overnight
12. filtrationfiltered under reduced pressure

ORD record

ord-9d368a09265b4add81b0b8fe7e34cc68

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08513411B2