Lithium Hexamethyldisilazide → (1S,5R)-5-Fluoro-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.2.0]heptane-1-carboxylic acid tert-butyl ester

A 1.0 M solution of lithium hexamethyldisilazide in tetrahydrofuran (5.02 mL) was added dropwise to a solution of (3S)-3-(2-bromoethyl)-4-fluoro-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (2.04 g, 4.92 mmol) in tetrahydrofuran (40 mL) in a nitrogen atmosphere at −72° C. over 10 minutes. The mixture was stirred at the same temperature for 15 minutes and then at 0° C. for 30 minutes. The reaction was quenched with a 10% citric acid solution (2 mL) and then poured into a mixture of ethyl acetate (100 mL) and a 10% citric acid solution (20 mL). After extraction with ethyl acetate (150 mL), the organic layer was washed with brine (20 mL×2), dried over anhydrous sodium sulfate, and filtered. The filtrate was then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give 1.41 g (86%) of the title compound as a white solid.

1. waitat 0° C. for 30 minutes
2. customThe reaction was quenched with a 10% citric acid solution (2 mL)
3. additionpoured into a mixture of ethyl acetate (100 mL)
4. extractionAfter extraction with ethyl acetate (150 mL)
5. washthe organic layer was washed with brine (20 mL×2)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationThe filtrate was then concentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1)

ORD record

ord-16fd1aeb6c6242dca4b63078c20a271c

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2