Ammonium Chloride → (S)-3-((R)-6-(4-Fluoro-3-methylbenzyloxy)-2-(4-fluoro-3-methylphenoxy)hex-4-enoyl)-4-isopropyloxazolidin-2-one

Temperature

-70 °C

To the solution of lithium bis(trimethylsilyl)amide (1.9 mL, 1.29 mmol, 1M in THF) in anhydrous 30 mL THF at −70° C. was slowly added over 15 minutes (S)-3-(2-(4-fluoro-3-methylphenoxy)acetyl)-4-isopropyloxazolidin-2-one (480 mg, 1.6 mmol) as a solution in 4.0 mL THF. The reaction mixture was stirred for 30 min at −70° C. and then was slowly added a pre-cooled solution of 1-Fluoro-4-((4-iodobut-2-enyloxy)methyl)-2-methylbenzene (1.0 g, 3.2 mmol) in 4 mL of THF. The resulting mixture was stirred at −70° C. for 1 h and the temperature was slowly raised over a period of 2 h. The mixture was poured into 40 mL saturated NH4Cl and extracted with ethyl acetate (3×40 mL). The combined organic layers were washed with brine (2×30 mL) and dried over Na2SO4. The solvent was removed under reduced pressure and the product isolated by Flash column chromatography eluting with 0% to 50% ethyl acetate/hexane to give 430 mg of the title compound as a light yellow oil.

1. stirringThe resulting mixture was stirred at −70° C. for 1 h
2. temperaturethe temperature was slowly raised over a period of 2 h
3. extractionextracted with ethyl acetate (3×40 mL)
4. washThe combined organic layers were washed with brine (2×30 mL)
5. dry with materialdried over Na2SO4
6. customThe solvent was removed under reduced pressure
7. customthe product isolated by Flash column chromatography
8. washeluting with 0% to 50% ethyl acetate/hexane

ORD record

ord-317066bb8d0246ae9979c5bde93a5d79

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07879911B2