Hydrochloric Acid → (2S)-1-[(tert-butoxy)carbonyl]-4,4-difluoropyrrolidine-2-carboxylic acid

Participants

Reaction Steps

40 mL of a 2 mol/L sodium hydroxide aqueous solution was added dropwise over a period of 4 minutes under ice cooling to a 152 mL methanol solution of 15.2 g of the compound obtained in step 3-2, after which the reaction mixture was stirred for 2.5 hours at the same temperature. Upon completion of the reaction, the methanol was distilled off under reduced pressure, 100 mL of chloroform was added to the aqueous layer thus obtained, and then 90 mL of 1 mol/L hydrochloric acid was added dropwise over a period of 6 minutes under ice cooling. Once it was confirmed that the aqueous layer was acidic, liquid separation was performed, and the aqueous layer was extracted with chloroform (30 mL×2). The combined organic layer was washed with 50 mL of saturated brine and dried with magnesium sulfate, then the drying agent was filtered off and the solvent was distilled off under reduced pressure to obtain 14.1 g of residue (white solid). The residue thus obtained was crystallized from diisopropyl ether/n-hexane to obtain 12.6 g of the titled compound (colorless crystals).

Provenance & Evidence