Citric Acid → HCID 67490916, Verbindung

Temperatur

-10 °C

A 1.8 M solution of lithium diisopropylamide in tetrahydrofuran (3.10 mL) was added dropwise to a solution of (3S)-3-[2-(tert-butyldimethylsilyloxy)ethyl]-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (2.24 g, 5.00 mmol) in tetrahydrofuran (20 mL) in a nitrogen atmosphere at −72° C. over five minutes. After stirring at the same temperature for 10 minutes, methyl iodide (0.34 mL, 5.50 mmol) was added. The mixture was stirred at the same temperature for 15 minutes and then heated to −10° C. over 10 minutes. Thereafter, a 10% citric acid aqueous solution (5 mL) was added. The reaction solution was poured into a mixture of ethyl acetate (100 mL) and 10% citric acid solution (50 mL), followed by extraction with ethyl acetate (200 mL). The organic layer was washed with brine (50 mL×2), dried over anhydrous sodium sulfate, and filtered. The filtrate was then concentrated under reduced pressure. The resulting dark brown residue was used for the next reaction without further purification.

1. stirringThe mixture was stirred at the same temperature for 15 minutes
2. extractionfollowed by extraction with ethyl acetate (200 mL)
3. washThe organic layer was washed with brine (50 mL×2)
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationThe filtrate was then concentrated under reduced pressure
7. customThe resulting dark brown residue was used for the next reaction without further purification

ORD-Eintrag

ord-e5d63454f6a74429adbefccb433a1bbd

Quelldatensatz

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08618094B2