Potassium Hydroxide → 1,2-Pyrrolidinedicarboxylic acid, 3-hydroxy-, 1-(1,1-dimethylethyl) 2-methyl ester, (2R,3S)-rel-

To a solution of 7B (18 g, 51.5 mmol) in anhydrous MeOH (360 mL) at RT was slowly added a freshly prepared 1N solution of KOH in anhydrous MeOH (77 mL, 77 mmol) in portions. The mixture was stirred at RT until the reaction was completed (about 1 hour). The reaction was cooled at 0° C., then quenched by slow addition of 1N aqueous HCl (77 mL). The mixture was concentrated under reduced pressure to remove most of the MeOH solvent, and the remaining mixture partitioned between water and EtOAc. The separated EtOAc phase was washed with saturated aqueous NaHCO3 and brine, dried over Na2SO4 and filtered. The filtrate was concentrated under reduced pressure to give a crude product, which was chromatographed eluting with 30% EtOAc/hexane to give 12.4 g of the title compound as a colorless oil.

1. custom(about 1 hour)
2. temperatureThe reaction was cooled at 0° C.
3. customquenched by slow addition of 1N aqueous HCl (77 mL)
4. concentrationThe mixture was concentrated under reduced pressure
5. customto remove most of the MeOH solvent
6. customthe remaining mixture partitioned between water and EtOAc
7. washThe separated EtOAc phase was washed with saturated aqueous NaHCO3 and brine
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure
11. customto give a crude product, which
12. customwas chromatographed
13. washeluting with 30% EtOAc/hexane

ORD record

ord-81591a03411f49b5bfb13e54a5236fac

Source dataset

uspto-grants-2003_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06670386B2