Ozone → (3S)-5-Oxo-3-(2-oxoethyl)-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

Temperature

-40 °C

A solution of (3S)-3-allyl-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (3.29 g, 10.0 mmol) in methanol (100 mL) was bubbled with ozone at −74° C. When the reaction solution turned blue, ozone bubbling was stopped and then the solution was bubbled with nitrogen at the same temperature. Sodium borohydride (568 mg) was added at the same temperature, and the mixture was stirred for 1.5 hours while heating to −40° C. The reaction solution was poured into a 10% citric acid solution (50 mL), and then the mixture was stirred sufficiently. The methanol component was evaporated, and then the aqueous layer was extracted with ethyl acetate (200 mL, 100 mL). The organic layer was washed with brine (50 mL×2), and then dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure into a slurry. Hexane was added to the resulting residue, and the slurry was stirred. The solid was collected by filtration and dried to give 1.70 g of the title compound as a white solid. The filtrate was concentrated, hexane was added to the resulting residue, and the slurry was stirred. The solid was collected by filtration to give 0.66 g of the title compound as a white solid. The same operation was repeated to give 0.35 g of the title compound as a white solid (total yield: 2.71 g, 82%).

1. customthe solution was bubbled with nitrogen at the same temperature
2. additionSodium borohydride (568 mg) was added at the same temperature
3. additionThe reaction solution was poured into a 10% citric acid solution (50 mL)
4. stirringthe mixture was stirred sufficiently
5. customThe methanol component was evaporated
6. extractionthe aqueous layer was extracted with ethyl acetate (200 mL, 100 mL)
7. washThe organic layer was washed with brine (50 mL×2)
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationAfter filtration
10. concentrationthe filtrate was concentrated under reduced pressure into a slurry
11. additionHexane was added to the resulting residue
12. stirringthe slurry was stirred
13. filtrationThe solid was collected by filtration
14. customdried

ORD record

ord-d985b494a54a4078974912e359417073

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2