Hydrochloric Acid → (2S)-3,3,3-Trifluoro-2-hydroxy-2-methylpropanoic acid

Participants

Reaction Conditions

Reaction Steps

Into a 500 ml three-necked round-bottomed flask equipped with a stirrer, a 1.0 M aluminum diisobutyl hydride/hexane solution (2400 ml, 2.40 mol) was charged in a nitrogen atmosphere. This solution was cooled to −80° C. A dichloromethane (600 g) solution of (S)-2,3-epoxy-2-trifluoromethylpropionic acid (149.82 g, 0.96 mol) was added over a period of two hours from a dropping funnel. After stirring at −70° C. for one hour, stirring was carried out at −50° C. for 6 hours. The reaction solution was cooled to −80° C., and a mixed solution of methanol (100 g) and dichloromethane (100 g) was dropwise added over a period of two hours to terminate the reaction. The reaction solution was dropwise added over a period of two hours to 1800 ml of a 18% HCl aqueous solution cooled to 0° C., and then, 160 g of sodium chloride was added. The mixture was extracted twice with 500 ml of diethyl ether, and the solvent was distilled off to obtain (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid (98.6 g) (yield: 65%). This was recrystallized twice from toluene (400 ml) to obtain (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid (51.6 g) having an optical purity of 99.9 ee % (yield: 34%). This product shows the same 1H and 13C-NMR and IR spectrum data as the already reported (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid and therefore was determined to be (S)-3,3,3-trifluoro-2-hydroxy-2-methylpropionic acid.

Provenance & Evidence