Hydrochloric Acid → (R)-4-(4-Chlorophenyl)pyrrolidin-2-one

Temperature

135 °C

Under a nitrogen atmosphere, to methanol (220 ml) was added methyl (3S,4R)-4-(4-chlorophenyl)-2-oxopyrrolidine-3-carboxylate (28.0 g, 110 mmol), and 2 mol/L sodium hydroxide aqueous solution (66 ml) was dropped over a period of 1 hour. After completion of dropping, the mixture was further stirred for 1 hour, and neutralized with 2 mol/L hydrochloric acid (71 ml), and methanol was distilled off under reduced pressure. The residue was extracted with ethyl acetate (150 ml×2), to obtain an ethyl acetate solution containing (3S,4R)-4-(4-chlorophenyl)-2-oxopyrrolidine-3-carboxylic acid. This solution was dropped over a period of 4 hours into xylene (150 ml) heated at 130 to 140° C. while distilling off ethyl acetate. After completion of the reaction, xylene (100 ml) was added, and the mixture was filtrated and concentrated under reduced pressure. Crystallization from xylene/heptanes was performed to obtain 19.3 g (98.6 mmol) of a title compound. Yield: 90%. The spectrum data corresponded to the value in non-patent document 1. The optical purity of the resultant title compound was measured by HPLC to find a value of 99% ee.

1. additionwas dropped over a period of 1 hour
2. distillationwas distilled off under reduced pressure
3. extractionThe residue was extracted with ethyl acetate (150 ml×2)
4. customto obtain an ethyl acetate solution
5. distillationwhile distilling off ethyl acetate
6. customAfter completion of the reaction, xylene (100 ml)
7. additionwas added
8. filtrationthe mixture was filtrated
9. concentrationconcentrated under reduced pressure
10. customCrystallization from xylene/heptanes

ORD record

ord-7ed5067296114a9da748e07abb1d68a6

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08293926B2