2-[3-(Trifluoromethyl)benzoyl]aminoacetic acid

2251-65-2

56-40-6

17794-48-8

GENERAL STEPS: In a 12 L four-necked round-bottomed flask equipped with a thermocouple controller, mechanical stirrer, heating jacket, condenser tube, and nitrogen inlet and outlet fittings, glycine (1, Alfa Aesar) (318 g, 4.19 mol), acetonitrile (1.2 L), and sodium hydroxide solution (5.31 L, 10.62 mol) were added. The mixture was cooled with stirring to 4°C. A solution of 3-(trifluoromethyl)benzoyl chloride (2, Alfa Aesar) (885.0 g, 4.12 mol) dissolved in acetonitrile (0.75 L) was added slowly and dropwise over a period of 2 h (1.39 L in total) while the internal temperature was controlled to be between 4-6°C. The mixture was then purified with a mixture of 2.5 g, 4.12 mol and 3-(trifluoromethyl)benzoyl chloride (2, Alfa Aesar). The resulting slightly orange-pink colored solution was continued to be stirred at 4°C for 30 min. The reaction mixture was acidified to pH=3 with concentrated hydrochloric acid (400 mL of 37% HCl solution was added over 30 min, keeping the temperature between 0-6°C) and stirred at 0°C for 1 h until a slightly pale yellow suspension was formed. The solid was collected by filtration, washed with cold (0°C) deionized water (300 mL x 2), dried in air for 2 h, and placed in a 60°C drying oven. Drying under room vacuum (120 mmHg) for 20 h gave pure 2-(3-(trifluoromethyl)benzoylamino)acetic acid (3) as an off-white solid. The filtrate was extracted with ethyl acetate (1 L x 2), and the combined organic phases were washed with brine (300 mL), concentrated to 66°C at room temperature, and then concentrated under high vacuum (20 mmHg) to give the crude product as an off-white waxy solid. The crude product was ground, sonicated with toluene (1 L) and stirred at 10°C for 1 hour. The solid was collected by filtration, washed with hexane (50 mL x 2) and dried in a vacuum oven at 50°C to give additional pure 2-(3-(trifluoromethyl)benzoylamino)acetic acid (3) as an off-white solid. The structure of product 3 was confirmed by 1H-NMR.