Ethyl(3R)-2-(4-chloro-2-fluorophenyl)-4,4,4-trifluoro-3-methylbutanoate → (3R)-2-(4-chloro-2-fluorophenyl)-4,4,4-trifluoro-3-methylbutanoic acid

Participants

Reaction Steps

4.26 g (13.6 mmol) of ethyl (3R)-2-(4-chloro-2-fluorophenyl)-4,4,4-trifluoro-3-methylbutanoate (diastereomer mixture) were dissolved in a mixture of 22 ml of methanol, 22 ml of THF and 11 ml of water, and 10.9 g of 50% strength aqueous sodium hydroxide solution were added at 0° C. The reaction mixture was stirred at RT overnight. Most of the organic solvents were then removed under reduced pressure. The mixture that remained was diluted with water and extracted with diethyl ether. After phase separation, the organic phase was discarded and the aqueous phase was acidified with semiconcentrated hydrochloric acid (pH about 2) and extracted repeatedly with ethyl acetate. The combined ethyl acetate phases were dried over sodium sulphate and concentrated under reduced pressure. This gave 3.38 g (76.7% of theory) of the target product as a mixture of diastereomers which could be used without further purification for subsequent reactions.

Provenance & Evidence