Lithium Hydroxide → 3-Oxo-3-{[3-(trifluoromethyl)phenyl]amino}propanoic acid

To a solution of 3-trifluoromethyl-phenylamine (11.6 mL; 93 mmol; 1 eq) and triethylamine (12.9 mL; 93 mmol; 1 eq) in dichloromethane (467 mL), methyl malonyl chloride (10.0 mL; 93 mmol; 1 eq.) is added at 0° C., under argon. The solution is allowed to stir for 10 minutes at room temperature. The crude mixture is then treated with water (115 mL) before removing the dichloromethane (15 mL) in vacuum. The resulting aqueous solution is cooled to 0° C. and diluted with methanol (235 mL) before adding dropwise a 1.5 M aqueous solution of LiOH (4.47 g; 186 mmol; 2 eq.). The solution is allowed to stir at room temperature for 1 hour. After removal of methanol under reduced pressure, the pH of the resulting aqueous solution is adjusted to 1 using a concentrated solution of HCl (16 mL). The acidic solution is extracted with dichloromethane (3×300 mL). The combined organic extracts are dried over sodium sulfate, filtered and concentrated under vacuum to afford the title compound as a white powder (21.8 g; 88 mmol; 95%).

1. custombefore removing the dichloromethane (15 mL) in vacuum
2. temperatureThe resulting aqueous solution is cooled to 0° C.
3. additiondiluted with methanol (235 mL)
4. stirringto stir at room temperature for 1 hour
5. customAfter removal of methanol under reduced pressure
6. extractionThe acidic solution is extracted with dichloromethane (3×300 mL)
7. dry with materialThe combined organic extracts are dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under vacuum

ORD record

ord-c4a4e6cfb68e46b3a6abd5885318cd8d

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08513250B2