Acetic Acid → (3S)-4-Fluoro-3-(2-hydroxyethyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester

Acetic acid (0.66 mL, 11.54 mmol) and a 1 M solution of tetrabutylammonium fluoride in tetrahydrofuran (8.3 mL, 8.3 mmol) were sequentially added to a solution of the crude (3S)-3-[2-(tert-butyldimethylsilyloxy)ethyl]-4-fluoro-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (3.44 g) in tetrahydrofuran in a nitrogen atmosphere at 0° C. After stirring at room temperature for 20 hours, the reaction solution was poured into a mixture of ethyl acetate (100 mL) and a saturated sodium bicarbonate solution (50 mL), followed by extraction with ethyl acetate (200 mL). The organic layer was washed with brine (50 mL×2), and then dried over anhydrous sodium sulfate and filtered. The filtrate was then concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1) to give 2.06 g (91%, two steps) of the title compound as colorless crystals.

1. extractiona saturated sodium bicarbonate solution (50 mL), followed by extraction with ethyl acetate (200 mL)
2. washThe organic layer was washed with brine (50 mL×2)
3. dry with materialdried over anhydrous sodium sulfate
4. filtrationfiltered
5. concentrationThe filtrate was then concentrated under reduced pressure
6. customThe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=1:1)

ORD record

ord-4453b5b9063c427fa3e131c3a6dce822

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2