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

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Reaction Steps

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%).

Provenance & Evidence