Hydrogen Peroxide → (S)-2-(4-bromophenyl)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)acetic acid

30% H2O2 (0.67 mL, 7.0 mmol) was added to a solution of LiOH—H2O (0.24 g, 5.60 mmol) in THF/water (2:1, 93 mL), and the solution was stirred at room temperature for 10 minutes. The solution was then cooled to 0° C. and treated with a solution of (S)-tert-butyl 5-((S)-2-((R)-4-benzyl-2-oxooxazolidin-3-yl)-1-(4-bromophenyl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate (1.60 g, 2.80 mmol) in THF (10 mL). The reaction was stirred at 0° C. for 2 hours and allowed to warm to room temperature and stirred overnight. The reaction was then cooled to 0° C. and treated with 1M Na2SO3 (10 mL) and stirred for 10 minutes. The reaction was then warmed to room temperature and stirred for 10 minutes. The reaction was next concentrated and extracted with EtOAc (2×20 mL). The aqueous layer was then acidified with 1N HCl to a pH of about 1 to about 2 and extracted with DCM (2×20 mL). The combined DCM fractions were dried over sodium sulfate, filtered, and concentrated to give (S)-2-(4-bromophenyl)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)acetic acid (1.01 g, 87% yield) as a solid. MS ESI (+) m/z 412 detected.

1. temperatureThe solution was then cooled to 0° C.
2. stirringThe reaction was stirred at 0° C. for 2 hours
3. temperatureto warm to room temperature
4. stirringstirred overnight
5. temperatureThe reaction was then cooled to 0° C.
6. stirringstirred for 10 minutes
7. temperatureThe reaction was then warmed to room temperature
8. stirringstirred for 10 minutes
9. concentrationThe reaction was next concentrated
10. extractionextracted with EtOAc (2×20 mL)
11. extractionextracted with DCM (2×20 mL)
12. dry with materialThe combined DCM fractions were dried over sodium sulfate
13. filtrationfiltered
14. concentrationconcentrated

ORD-Eintrag

ord-1e6a07b18e6847bea1324a24aa3862d3

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08372842B2