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

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

Melting point:

134-138°C

Boiling point:

401.7±45.0 °C(Predicted)

Density 

1.417±0.06 g/cm3(Predicted)

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

pka

3.69±0.10(Predicted)

Appearance

White to light yellow Solid

CAS DataBase Reference

17794-48-8(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

HazardClass 

IRRITANT

HS Code 

2924297099

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H319Causes serious eye irritation

Precautionary statements

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

2-[3-(Trifluoromethyl)benzoyl]aminoacetic acid Chemical Properties,Usage,Production

Definition

ChEBI: M-Trifluoromethylhippuric acid is a N-acylglycine. It is functionally related to a N-benzoylglycine.

Synthesis

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.

References

[1] Patent: US2010/144695, 2010, A1. Location in patent: Page/Page column 61-62
[2] Patent: EP2452939, 2012, A2. Location in patent: Page/Page column 17
[3] Patent: US2012/190689, 2012, A1. Location in patent: Page/Page column 11-12
[4] Patent: US2005/192302, 2005, A1. Location in patent: Page/Page column 21
[5] Patent: WO2012/114223, 2012, A1. Location in patent: Page/Page column 36