4'-Amino-3'-chloro-5'-(trifluoromethyl)acetophenon Chemical Properties

Melting point:

132-134℃

Boiling point:

288℃

Density 

1.408

Flash point:

128℃

storage temp. 

under inert gas (nitrogen or Argon) at 2–8 °C

solubility 

Chloroform (Slightly), Methanol (Slightly)

form 

Solid

color 

White to Pale Brown

4'-Amino-3'-chloro-5'-(trifluoromethyl)acetophenon Usage And Synthesis

Chemical Properties

Off-White Solid

Uses

Mabuterol intermediate.

Synthesis

General procedure for the synthesis of 1-[4-amino-3-chloro-5-(trifluoromethyl)phenyl]ethanone from 3-chloro-5-(trifluoromethyl)benzoyl chloride and diethyl malonate: 1.31 g (0.0535 mol) of magnesium shavings, 1.6 mL of anhydrous ethanol and 0.12 mL of carbon tetrachloride were added to the reaction flask at room temperature. The reaction mixture was heated and reflux was maintained at an absolute pressure of 14.6 mL while tetrahydrofuran was slowly added. A mixture of 8.1 mL (0.0534 mol) diethyl malonate, 4.8 mL of anhydrous ethanol, and 5.6 mL of tetrahydrofuran was added dropwise over a period of 1 h under continuous reflux and stirring, followed by continued reflux for 2 h. The reaction mixture was then purified with a mixture of 2.5 g (0.0534 mol) of carbon tetrachloride. 13.1 g (0.051 mol) of 4-amino-3-chloro-5-trifluoromethylbenzoyl chloride was dissolved in 43.5 mL of tetrahydrofuran and added dropwise to the above reaction solution over 0.5 hours. After dropwise addition, reflux was continued for 2 hours. After completion of the reaction, it was cooled to room temperature and the pH was adjusted dropwise to 2 by addition of 2N sulfuric acid solution. the organic phase was separated and evaporated under reduced pressure to give an oily product. A mixture of 45.8 mL of glacial acetic acid, 30.6 mL of water and 5.7 mL of concentrated sulfuric acid was added to the oily product and heated to reflux for 5 hr. The solvent was removed by evaporation under reduced pressure and the solid obtained was dissolved in chloroform.

References

[1] Patent: EP1439164, 2004, A1. Location in patent: Page 4
[2] Journal of Labelled Compounds and Radiopharmaceuticals, 2010, vol. 53, # 13, p. 779 - 781

4'-Amino-3'-chloro-5'-(trifluoromethyl)acetophenon(97760-76-4)Related Product Information

• 4-AMINO-3-CHLORO-5-(TRIFLUOROMETHYL)BENZALDEHYDE
• 3'-CHLORO-5'-(TRIFLUOROMETHYL)ACETOPHENONE
• 4'-Amino-3'-chloro-5'-(trifluoromethyl)acetophenon